Hb G-CHINESE: A G → C SUBSTITUTION AT CODON 30 OF THE α2-GLOBIN GENE CREATES A PstI CUTTING SITE

We used magnetic resonance imaging (MRI) to compare the effect of iron chelation on liver, spleen and bone marrow. We examined 21 β-thalassemic patients undergoing deferoxamine (DFO) (9/21) or combined therapy [DFO and deferiprone (L1), 12/21] with two abdominal MRI studies using T1-w/Pd-w/T2*-wGRE and T1-wTSE sequences. Changes in serum ferritin (DF%), and liver, spleen and marrow to paraspinous muscles signal intensity ratios (SI) in T1-wTSE sequence were calculated as D%=[(2^ndvalue-1^st value)/1^st value] ×100%. Negative DF% and positive D(SI)% indicated reduction of iron. Although 17/21 (80.9%) patients demonstrated reduction in ferritin, only 8/21 (38%), 7/21 (33.3%) and 7/21 (33.3%) patients had decreased liver, spleen and marrow iron. Patients undergoing combined therapy showed significantly greater reduction (Student's t-test, p < 0.05) or less increase (t-test, p <0.05) in iron stores. Combined therapy is more effective than DFO for removing and preventing liver, spleen and bone marrow iron accumulation in β-thalassemic patients. Magnetic resonance imaging is valuable for organ-specific monitoring of chelation therapy.     

Further Identification of The Hyperunstable α-Globin Chain Variant Hb Heraklion [codons 36/37 (–CCC); Pro→0 (α1)] in Greek Cases With Co-Inherited α+-Thalassemia Mutations

We report four Greek cases (from three unrelated families), who all had a similar atypical thalassemia intermedia phenotype, characterized by chronic moderate anemia, mild hemolysis and splenomegaly in the absence of abnormal hemoglobin (Hb) fractions. In all four cases (two unrelated children and two siblings), DNA analysis identified common α⁺-thalassemia (α⁺-thal) mutations in trans to the in frame 3 bp deletion (?CCC) on the α1-globin gene between codons 36 and 37, which has previously been reported as Hb Heraklion in a single Greek case. Clinical, hematological and biochemical findings in all cases, including a follow-up evaluation of the original case, are described. All the cases originated from the Greek island of Crete.     

Effective Combination Therapy of Deferiprone and deferoxamine for the Rapid Clearance of Excess Cardiac IRON and the Prevention of Heart Disease in Thalassemia. The Protocol of the International Committee on Oral Chelators

The International Committee on Oral Chelators (ICOC) combination therapy protocol involving the administration of deferiprone (L1) during the day (80–110 mg/kg/day) and deferoxamine (DFO) (40–60 mg/kg at least 3 days/week) during the night for 8–12 hours using a pump, or the whole 24 hours using an elastomeric pump infuser, has been tested in 11 thalassemia patients (seven males, four females) over a period of 9–28 months. The patients had variable serum ferritin levels (0.54–4.6 mg/L) and cardiac iron load ranging from normal to severe siderosis levels (MRI T2*: 4.7–45 ms). There was a substantial overall reduction in serum ferritin levels (0.17–2.16 mg/L) and normalization of cardiac iron (MRI T2* >20 ms) in all patients. In two patients with severe and moderate cardiac iron load range levels, cardiac iron normalization was achieved within 9–10 months. Two patients on L1 monotherapy (80–120 mg/kg/day) maintained normal range MRI T2* cardiac iron levels over the same period. The ICOC combination therapy protocol appears to be the most effective and least cumbersome form of chelation treatment for the rapid clearance of excess iron from the heart.     

Thalassemia Treatment and Prevention in Uva Province,Sri Lanka: A Public Opinion Survey

Due to its excessive cost thalassemia management is a major health care problem in Sri Lanka. The majority of doctors are using only desferrioxamine (DFO), in grossly inadequate doses mainly because of its unavailability. Deferiprone (L1), which is more affordable, is not used due to fear of toxicity, as previously reported. Arthropathy attributed to L1 has been observed in some patients, and has led to the discontinuation of the drug in all patients, without scientific rationale. The proposed thalassemia prevention project for Uva Province is based on prevention of marriages between carriers. This could be achieved by carrier screening and counseling of teenagers and adolescents well before they select their partners.

In Sri Lanka, people find their marriage partners at their work place or universities, by themselves, or with the help of professional marriage brokers (they are called Kapuwa), through relatives and close friends. This process of finding a partner may also be helped by paper advertisements. However, in addition to the appearance and attitude of the prospective partner, the caste, social background and horoscope are major considerations in selecting a partner. Even when they select partners on their own at the work place or university, they keep these factors in the back of their minds to ensure social acceptance. Many relationships are given up due to objections and advice from parents when the caste or social background does not match. A horoscope is a written document that almost every child gets, written by a professional horoscope reader and depending on the time of birth. It is believed, according to the horoscope, that a person's attitudes, desires, future prospects of finding a suitable partner, could be predicted. It is rare to proceed with a marriage if the horoscope does not match. These customs are considered less seriously among educated people when they find their partner at the work place or university.

The concept of thalassemia risk-free marriages advocates promotion of marriages where at least one partner is a non-carrier. Success of such a project could be monitored at the time of marriage. This opinion survey indicates that the public is motivated to promote carrier screening and the prevention of thalassemia.     

Thalassemia Trait in Outpatient Clinics of Sana'a City,Yemen

Blood samples were collected from 699 patients attending out patient clinics in Sana'a City, Yemen, to obtain some idea of the prevalence of the thalassemias in our country. Complete blood count, hemoglobin (Hb) electrophoresis, quantitation of Hb A₂ and Hb F, and serum ferritin were determined. Microcytic, hypochromic red cells were found in 103 subjects (14.7%). Iron deficiency alone accounted for only a small proportion of these (n = 12), whereas features suggestive of β‐thalassemia (β-thal) were present in 31 patients (4.43%) and features suggestive of α-thal trait were found in 60 patients (8.6%). The study showed that thalassemia probably accounts for most red cell microcytosis in these out patient clinics, and could represent a significant health problem through births of homozygotes and compound heterozygotes with severe disorders. This pilot study should be repeated with improved technology, and extended to include globin gene analysis to define the nature of the disorders that remain poorly diagnosed.     

Thrombosis in Thalassemia: Why are we so Concerned?

Although life expectancy of thalassemia patients has markedly improved over the last few decades, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events (TEE), mainly in β-thalassemia intermedia (β-TI), has led to the identification of a hypercoagulable state in these patients. In this review, the molecular and cellular mechanisms leading to hypercoagulability in thalassemia are highlighted, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemia. Clinical experience and available clues on optimal management are also discussed.     

Iron Overload,Cardiac and Other Factors Affecting Pregnancy in Thalassemia Major

The reproductive thalassemic population is growing older and doctors confront the challenge of the thalassemic pregnancy. Pregnancy is characterized by dynamic multiple system changes, resulting in increased basal oxygen consumption, changes in energy substrate use by different organs and increased susceptibility to oxidative stress, while homozygous transfusion-dependent β-thalassemia (β-thal) patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Pregnant thalassemic patients require significantly larger amount of total blood transfusion during pregnancy and iron overload increases the oxidative stress of pregnancy, while the risk for cardiovascular events, in a high cardiac output state, is augmented and chelation treatment is generally avoided due to the potential teratogenicity. Pregnancy in thalassemia major should be considered high risk, and be cared for by an expert team with special caution and sensitivity.     

Thalassemia Syndromes in Serbia: An update

Thalassemia syndromes constitute a group of genetic disorders, widespread throughout the world. The present study contains data on thalassemia syndromes and their chromosomal environment obtained in Serbia over a period of 10 years. Ten different β-thalassemia (β-thal) mutations and two hemoglobin (Hb) variants were detected in 127 members of 68 families. Hb Lepore-Boston-Washington (Lepore-BW) (δ87Gln-β-IVS-II-8), a thalassemic Hb variant, was shown to be the most common cause of thalassemia in Serbia.

Haplotype analyses of the β-globin gene clusters of healthy individuals as well as of individuals affected with β-thal showed that haplotype I was the most frequent haplotype in the Serbian population, followed by haplotypes II and IX. Two novel haplotypes were detected. Haplotype analyses showed the association between certain haplotypes and the most common thalassemic mutations. Results presented in this paper will update the Serbian national mutation database and contribute to a better understanding of genographic history of South European and Balkan populations.     

Early detection of cardiac involvement in thalassemia: From bench to bedside perspective

Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chelation is given to patients,the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition.Various direct and indirect methods of iron assessment,including serum ferritin level,echocardiogram,non-transferrin-bound iron,cardiac magnetic resonance T2*,heart rate variability,and liver biopsy and myocardial biopsy,have been proposed for early detection of cardiac iron overload in TM patients.However,controversial evidence and limitations of their use in clinical practice exist.In this review article,all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented.Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients,these two methods are also presented and discussed.The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed.     

Spinal cord compression secondary to extramedullary hematopoiesis in thalassemia intermedia

Extramedullary hematopoiesis associated with thalassemia causing spinal cord compression is an extremely rare event in the course of the disease. Documentation with an imaging technique, such as MRI, is mandatory. A patient with thalassemia intermedia, who developed paraparesis in spite of transfusion, underwent surgical decompression. Rapid neurological improvement was observed postoperatively and this neurological condition was protected with adequate hemoglobin level. Management of these patients remains controversial. Various modes of therapy such as surgical decompression, radiotherapy, and transfusion are discussed and the related literature is reviewed. Received: 11 October 1997 Revised: 28 April 1998 Accepted: 15 May 1998