In South Asians
Hydrops Fetalis could occur in offsprings.
In African Americans
Hemoglobin H (--/-ๅ)
Moderately severe anemia with splenomeglay, microcytosis
demonstrable by speical staining of hgb electrophoresis
Hydrops Fetalis (--/--)
Incompatible with life
There is reduced or absent beta-globulin synthesis. This results in free alpha-globulin accumulations, which precipitate during early erythroblast development because of the relative insolubility of free alpha chains.
Because of the above mentioned defect, ineffective erythropoiesis enues. There is also increased destruction of the peripheral red blood cells. Therefore, patients develop splenomegaly (with hypersplenism, & skeletal & soft tissue changes associated with an expanded bone marrow. Some of these include osteoporosis, iron overload, and extramedullary hematopoiesis.
Diagnosis of beta-thalassemia:
Shared features- microcytosis, hypochromia, poikilocytosis.
Clinical Spectrum- asymptomatic to intrauterine death
b-thal minor (Beta thal) +
One b-chain defective Microcytosis, target cells, mild-moderate anemia (30's) Hgb electrophoresis
b-thal major (Beta ) o
Two Beta-chains defective Severe anemia, hemolysis Hgb electrophoresis
b-thal intermediate (Beta ) -
Two Beta-chains defective with some normal b-chain
production Variable between minor and major thal
Blood 2000 Nov 15;96(10):3357-63 Related Articles, Links
Oral isobutyramide reduces transfusion requirements in some patients with homozygous beta-thalassemia.
Reich S, et al.
The butyrate derivative isobutyramide (IBT) increases HbF in patients with beta-hemoglobinopathies, but little is known about its usefulness for prolonged therapeutic use. We treated 8 patients with transfusion-dependent beta-thalassemia with 350 mg/kg/d of oral IBT for 126-384 days. During the trial period, the hgb level was maintained between 85 g/L (range 82-87 g/L) (pretransfusion) & 115 g/L (range 110-119 g/L) (post-transfusion) (median, interquartile range), corresponding to 4-week transfusion intervals in all patients during the pretreatment phase. Adverse effects (bitter taste, epigastric discomfort) did not cause discontinuation of IBT. HbF increased in all patients from 3.1% (range 1.9%-4.8%) to 6.0% (range 3.3%-8.7) (P =.0017), while free Hb dropped from 0.48 g/L (range 0.39-0.81 g/L) to 0.19 g/L (range 0.16-0.24 g/L) (P <.0001). Transfusion intervals were consistently extended to 8 or 9 weeks in 1 patient, resulting in a decrease of daily iron load from 455 microgram/kg per day (range 451-459 microgram/kg per day) before therapy to 211 microgram/kg per day (range 203-286 microgram/kg per day) during the 12-month treatment period. Prolongation of transfusion intervals achieved by IBT was less consistent in another patient, whose parenteral iron load nevertheless decreased from 683 microgram/kg per day (range 618-748 microgram/kg per day) to 542 microgram/kg per day (340-596 microgram/kg per day). In the other 6 patients, no prolongation of transfusion intervals was achieved. Response to treatment was associated with high pretreatment HbF (> 4.5%), high parental HbF, and increased erythropoietin levels (> 150 IU/L). We conclude that IBT prolongs transfusion intervals and reduces parenteral iron burden in some patients with transfusion-dependent beta-thalassemia.
Blood Cells Mol Dis 2000 Oct;26(5):453-66
Reduction of the clinical severity of sickle cell/beta-thalassemia with hydroxyurea: the experience of a single center in Greece.
Loukopoulos D, et al.
The use of hydroxyurea for the prevention of sickle cell crises in patients with homozygous HbS disease is now well established. The beneficial effects of this compound stem from (a) selective enrichment of red cells containing an increased amount of fetal hemoglobin, which inhibits HbS polymerization, and (b) a decrease of leukocytes, platelets, and reticulocytes, which significantly limits their adherence to the vascular wall. We report the results of a clinical trial of hydroxyurea on 55 Greek-origin patients with sickle cell/beta-thalassemia and 14 patients with homozygous HbS disease who have been treated with hydroxyurea for several years. Such patients have a higher probability to benefit from hydroxyurea therapy, since in addition to its antisickling effect, the increase of gamma-chain synthesis is expected to diminish the deleterious effects of the unbound alpha-globin chains. Selection of patients and monitoring throughout the whole trial were done by the same clinicians. Quantitative expression of the clinical condition was done using a system scoring several outcome parameters. For a period of 52 months prior to starting treatment, the total score of severity for 59 evaluable patients was 1182 points (3068 patient-weeks), while for the 12,018 patient-weeks of the trial this parameter fell to only 82 points. Other observations of interest include the significant improvement of a group of patients with hepatic cholestasis, the development of leg ulcers possibly related to the treatment, and the dramatic increase of hemoglobin F, often in association with an increase of the total hemoglobin levels as a result of decreased hemolysis.
Hematol J 2000;1(5):295-300
Increased erythropoietin level induced by hydroxyurea treatment of sickle cell patients.
Papassotiriou I, et al.
Administration of hydroxyurea in sickle cell disease is associated with a dramatic increase of HbF along with a significant clinical improvement and, occasionally, increased total hemoglobin levels. The underlying mechanisms are not yet fully elucidated. We report the response of 3 patients with homozygous sickle cell disease & 10 patients with compound HbS/beta-thalassemia (4 with beta(o)thal/HbS & 6 with beta(+)thal/HbS respectively) to hydroxyurea treatment with regards to their serum erythropoietin levels (sEpo). RESULTS: Baseline sEpo levels varied from 33.0 to 284.0 IU/L & showed a significant negative correlation with the respective Hb values (P<0.007). 2-3 weeks after initiation of treatment, the sEpo values started to increase & reached levels 3-31X higher than the baseline 2-3 weeks later. Thereafter, in most cases the Epo values decreased and remained at intermediate levels throughout the rest of hydroxyurea administration, while in a few cases, they returned to baseline. An inappropriate increase of sEpo following treatment with various cytostatic drugs, independently of anemia induced by cytostatic agents, has already been reported in the literature. The cytostatics included cyclophosphamide, anthracyclines, cytosine arabinoside etc., but not hydroxyurea. The results described here with hydroxyurea are virtually similar, ie, they show a significant sEpo increase 5-10 days post therapy with no apparent cause. Pulses of high dose Epo have been reported to promote proliferation of erythroid precursors with HbF synthesizing capacity. CONCLUSION: Our hypothesis is that a similar phenomenon may occur here also, in the sense that peaks of endogenous Epo may promote proliferation of erythroid precursors which maintain the capacity to synthesize HbF