Hb TAYBE: clinical and morphological findings IN 43 patients.

UNLABELLED: Hereditary sequence variants in globin genes are usually silent and are rarer in α-globin chains than ß-globin chains. Some may lead to an unstable protein with a hemolytic or thalassemic phenotype. Hb Taybe is an unstable α-chain hemoglobin variant caused by the deletion of a threonine residue at codon 38 or 39 of the α1 globin gene. This deletion results in a structural abnormality that affects the α1 ß2 contact and the α1 ß1 interface, producing a highly unstable Hb. OBJECTIVE: We describe the clinical, laboratory, and morphological characteristics of 43 patients with Hb Taybe, sixteen of whom are heterozygous, eight are homozygous, and nineteen are double heterozygous for Hb Taybe and other α-gene mutations or deletions. RESULTS: The clinical presentation is very variable from a mild hemolytic anemia to the need for red cell transfusion. Morphological characteristics include erythroid hyperplasia, defective hemoglobin production, and dyserythropoietic features. On electron microscopy dyserythropoiesis and cytoplasmic precipitation of globin compatible optical dense material is seen. CONCLUSIONS: This is the largest report of Hb Taybe patients. Previous reported cohorts are not related to these cases. We conclude that patients carrying Hb Taybe have a unique hematological and clinical phenotype distinct from other hemoglobinopathies and from congenital dyserythropoietic anemia.

Sickle cell anemia in northern Israel: screening and prevention.

BACKGROUND: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the beta globin molecule. About 80 patients with SCA in northern Israel are currently receiving treatment. OBJECTIVES: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA. METHODS: Since 1987, screening for beta thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others. RESULTS: During the 20 year period 1987-2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 +/- 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion. CONCLUSIONS: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect beta thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant despite the low incidence of the S gene in our population, namely < 1%.

Response to hydroxyurea therapy in beta-thalassemia.

Although a relatively small number of previous studies suggest a modest response to hydroxyurea (HU) therapy in beta-thalassemia, more recent investigations have revealed that some transfusion-dependent patients can become transfusion-independent following HU therapy. Patients with Ggamma XmnI polymorphism, several beta-globin mutations, and alpha-thalassemia deletions were inconsistently reported to have significant responses to HU therapy. To better predict who may respond, we retrospectively evaluated the clinical response and the molecular background of 18 beta-thalassemia patients treated with HU for a mean of 46 months. The majority of transfusion-dependent patients responded to HU therapy with 9 out of 11 (82%) becoming transfusion-independent. Five thalassemia intermedia (TI) patients receiving occasional blood transfusion did not require any additional transfusions following therapy and two TI patients who had never received transfusions had a 2 g/dl increase in their hemoglobin level. The majority of beta-thalassemia major patients who became transfusion-independent (7/9) were either homozygous (5) or heterozygous (2) for the XmnI polymorphism. No correlation was identified between response to therapy and the presence of specific beta-thalassemia mutations or alpha-globin deletions. We conclude that further analysis of the degree of response of transfusion-dependent beta-thalassemia patients to HU therapy, as well as, the impact of their genetic background on this response is required to identify patients likely to have significant response.

Prevention of ß Thalassemia in Northern Israel - a Cost-Benefit Analysis.

BACKGROUND: ß Thalassemia major is characterized by hemolytic anemia, ineffective erythropoiesis and hemosiderosis. About 4% of the world population carries a Thalassemia gene. Management includes blood transfusions and iron chelation. However, this treatment is costly, and population screening may be significantly more cost beneficial. PURPOSE: The purpose of the current study is to analyze the cost of running a prevention program for ß Thalassemia in Israel and to compare it to the actual expenses incurred by treating Thalassemia patients. METHODS: THREE COST PARAMETERS WERE ANALYZED AND COMPARED: the prevention program, routine treatment of patients and treatment of complications. An estimation of the expenses needed to treat patients who present with complications was calculated based on our ongoing experience in treating deteriorating patients. RESULTS AND CONCLUSIONS: The cost of preventing one affected newborn was $63,660 compared to $1,971,380 for treatment of a patient during 50 years (mean annual cost: $39,427). Thus, the prevention of 45 affected newborns over a ten year period represents a net saving of $88.5 million to the health budget. Even after deducting the cost of the prevention program ($413.795/year), the program still represents a benefit of $76 million over ten years. Each prevented case could pay the screening and prevention program for 4.6 years.