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Ali T. Taher - One of the best experts on this subject based on the ideXlab platform.
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digital thermography and vascular involvement in β Thalassemia Intermedia
Annals of Hematology, 2021Co-Authors: Farah Abdulhai, Ali T. Taher, Rayan Boufakhredin, Miran A Jaffa, Joseph Elias, Patrick Zakka, Mostafa Hotait, Samir Arnaout, Marwan M RefaatAbstract:Beta-Thalassemia Intermedia (β-TI) is associated with vascular dysfunction. We used digital thermal monitoring (DTM), a non-invasive tool that evaluates vascular function based on changes in fingertip temperature during and after cuff occlusion on β-TI patients. Thirty-three patients (18 years and older) were recruited in this study and divided into 3 groups: Thalassemia, anemic controls, and healthy controls. Exclusion criteria included factors that are known to be associated with vascular damage. Patients underwent DTM and results were extracted as vascular reactivity index (VRI), a measure of how well the circulatory system responds to stimuli that require adjustments of blood flow. One-way analysis of variance (ANOVA) was used to test the mean difference in VRI between the 3 groups. A multiple linear regression was also carried out with VRI as the outcome of interest and a function of covariates that were thought to be of clinical relevance to VRI. The frequency, mean VRI ± standard error (SE) for the thalassemic group were (N = 16), mean = 2.243 ± 0.111; for anemic controls (N = 9), mean = 2.374 ± 0.162; and for the controls (N = 8), mean = 2.338 ± 0.092. ANOVA test indicated a non-significant difference in mean VRI between the three groups (P value = 0.731). Multiple linear regression couldn’t detect any significant association between VRI and any of the predictors including the groups. Our study did not show a significant difference in VRI between the 3 study groups. Prospective studies of larger sample size are warranted to establish DTM as a possible non-invasive tool used to evaluate vascular function in β-TI patients.
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revisiting beta Thalassemia Intermedia past present and future prospects
Hematology, 2017Co-Authors: Naouel Ben Salah, Rayan Boufakhredin, Fethi Mellouli, Ali T. TaherAbstract:ABSTRACTBackground: The spectrum of Thalassemias is wide ranging from Thalassemia minor, which consists of mild hypochromic microcytic anemia without obvious clinical manifestations, to Thalassemia major (TM), which is characterized by severe anemia since the first years of life and is transfusion dependent. Thalassemia Intermedia (TI) describes those patients with mild or moderate anemia.Objective: To describe the genetic features and major clinical complications of TI, and the therapeutic approaches available in the management of this disease.Methods: Publications from potentially relevant journals were searched on Medline.Results and discussion: Over the past decade, the understanding of TI has increased with regard to pathophysiology and molecular studies. It is now clear that clinical presentation and specific complications make TI different from TM. It is associated with greater morbidity, a wider spectrum of organ dysfunction and more complications than previously thought.Conclusion: TI is not a mi...
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guidelines for diagnosis and management of beta Thalassemia Intermedia
Pediatric Hematology and Oncology, 2014Co-Authors: Mehran Karimi, Naji S Mallat, Nader Cohan, V De Sanctis, Ali T. TaherAbstract:Beta-Thalassemia Intermedia (β-TI) is a genetic variant of beta-Thalassemias with a clinical disorder whose severity falls between Thalassemia minor and Thalassemia major. Different genetic defects are involved in this disorder and, based on severity of disease, clinical complications like skeletal deformities and growth retardation, splenomegaly, extramedullary hematopoiesis, heart failure, and endocrine disorders may be present in untreated patients. Precise diagnosis and management are essential in these patients for prevention of later clinical complications. Diagnosis of TI is based on clinical and laboratory data. There are some treatment strategies like modulation of gamma-globulin chain production with hydroxyurea or other drugs, transfusion, splenectomy, and stem cell transplantation. Iron chelation therapy is also needed in many of these patients even if they are not transfused. The aim of this manuscript is to review the clinical manifestations, complications, genetic defects, and unmet treatments needs in TI.
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serum ferritin level and morbidity risk in transfusion independent patients with β Thalassemia Intermedia the orient study
Haematologica, 2014Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Mehran Karimi, Giovanna Graziadei, Amal Elbeshlawy, Shahina Daar, Matthew Magestro, Jerome Wulff, Guilhem Pietri, Ali T. TaherAbstract:Similar to other forms of non-transfusion-dependent Thalassemia, the diagnosis of β-Thalassemia Intermedia is associated with a state of iron overload.[1][1]–[3][2] This occurs in the absence of regular transfusion therapy and is primarily attributed to increased intestinal iron absorption
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β Thalassemia Intermedia a bird s eye view
Turkish journal of haematology : official journal of Turkish Society of Haematology, 2014Co-Authors: Anthony Haddad, Paul Tyan, Amr Radwan, Naji S Mallat, Ali T. TaherAbstract:Beta-Thalassemia is due to a defect in the synthesis of the beta-globin chains, leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. The spectrum of Thalassemias is wide, with one end comprising Thalassemia minor, which consists of a mild hypochromic microcytic anemia with no obvious clinical manifestations, while on the other end is Thalassemia major, characterized by patients who present in their first years of life with profound anemia and regular transfusion requirements for survival. Along the spectrum lies Thalassemia Intermedia, a term developed to describe patients with manifestations that are neither mild enough nor severe enough to be classified in the spectrum's extremes. Over the past decade, our understanding of β-Thalassemia Intermedia has increased tremendously with regards to molecular information as well as pathophysiology. It is now clear that β-Thalassemia Intermedia has a clinical presentation as well as complications associated with the disease that are different from those of β-Thalassemia major. This review is designed to tackle issues related to β-Thalassemia Intermedia from the basic definition of the disease to paramedical issues, namely the quality of life in these patients. Genetics and pathophysiology are revisited, as well as the complications specific to this disease. These complications include effects on several organ systems, including the cardiovascular, hepatic, endocrine, renal, brain, and skeletal systems. Extramedullary hematopoiesis is also discussed in this article. Risk factors are highlighted and cutoffs are identified to minimize morbidities in β-Thalassemia Intermedia. Several treatment modalities are considered by shining a light on the pros and cons of each modality, as well as the role of special pharmacological agents in the progress of the disease and its morbidities. Finally, health-related quality of life is discussed in these patients with a direct comparison to the more severe β-Thalassemia major.
Maria Domenica Cappellini - One of the best experts on this subject based on the ideXlab platform.
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bone quality in beta Thalassemia Intermedia relationships with bone quantity and endocrine and hematologic variables
Annals of Hematology, 2017Co-Authors: Marina Baldini, Maria Domenica Cappellini, Alessia Marcon, Fabio Massimo Ulivieri, Sonia Seghezzi, Ramona Cassin, Carmelo Messina, Giovanna GraziadeiAbstract:We report the first evaluation of bone quality in 70 Thalassemia Intermedia (TI) patients (37 males, 33 females, age 41 ± 12 years). Thirty-three patients (47%) had been transfused, 34 (49%) had been splenectomized, 39 (56%) were on iron chelation therapy, and 11 (16%) were on hydroxyurea. Mean hemoglobin was 9.2 ± 1.5 g/dl, median ferritin 537 ng/dl (range 14–4893), and mean liver iron concentration 7.6 ± 6.4 mg Fe/g dw. Fifteen patients (21%) had endocrinopathies, and 29 (41%) had vitamin D deficiency. Bone quantity (bone mineral density, BMD) and bone quality (trabecular bone score, TBS) were evaluated by densitometry. In 53/70 patients (76%), osteopathy was found (osteoporosis in 26/53, osteopenia in 27/53). BMD values were higher in the never-transfused patients and in the not-chelated group. A highly significant correlation was found between splenectomy and BMD at all the sites, with lower values in the splenectomized patients. TBS values were significantly lower in TI patients than in 65 non-thalassemic controls (1.22 vs 1.36, p < 0.01), mainly in those splenectomized and in the transfused and chelated groups (p < 0.01). TBS did not correlate with liver iron concentration values. Our data disclose the major role of non-invasive bone quality evaluation in TI patients, especially those with the worst health state, to obtain a comprehensive assessment of fracture risk. Splenectomy seems to play a major part in bone complications.
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serum ferritin level and morbidity risk in transfusion independent patients with β Thalassemia Intermedia the orient study
Haematologica, 2014Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Mehran Karimi, Giovanna Graziadei, Amal Elbeshlawy, Shahina Daar, Matthew Magestro, Jerome Wulff, Guilhem Pietri, Ali T. TaherAbstract:Similar to other forms of non-transfusion-dependent Thalassemia, the diagnosis of β-Thalassemia Intermedia is associated with a state of iron overload.[1][1]–[3][2] This occurs in the absence of regular transfusion therapy and is primarily attributed to increased intestinal iron absorption
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evaluation of the 5mg g liver iron concentration threshold and its association with morbidity in patients with β Thalassemia Intermedia
Blood Cells Molecules and Diseases, 2013Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Ali T. TaherAbstract:Iron overload may still occur in transfusion-independent patients with β-Thalassemia Intermedia due to increased intestinal iron absorption. In this study, we evaluated the association between iron overload, using a liver iron concentration threshold of therapeutic significance (≥5mg/g), and morbidity in 168 chelation naive patients with β-Thalassemia Intermedia. We demonstrated that patients with a liver iron concentration ≥5mg/g have a significantly higher prevalence of several serious vascular and endocrine/bone morbidities than do patients with <5mg/g, and we established absolute morbidity risk values differentiating both groups. We also demonstrated that the association between iron overload and morbidity in such patients is independent of the effects of advancing age and disease severity. These findings suggest that treating iron burden in β-Thalassemia Intermedia may be associated with reduction in serious morbidity risk.
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evaluation of the 5mg g liver iron concentration threshold and its association with morbidity in patients with β Thalassemia Intermedia
Blood Cells Molecules and Diseases, 2013Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Ali T. TaherAbstract:Abstract Iron overload may still occur in transfusion-independent patients with β-Thalassemia Intermedia due to increased intestinal iron absorption. In this study, we evaluated the association between iron overload, using a liver iron concentration threshold of therapeutic significance (≥ 5 mg/g), and morbidity in 168 chelation naive patients with β-Thalassemia Intermedia. We demonstrated that patients with a liver iron concentration ≥ 5 mg/g have a significantly higher prevalence of several serious vascular and endocrine/bone morbidities than do patients with
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hepatocellular carcinoma in hepatitis negative patients with Thalassemia Intermedia a closer look at the role of siderosis
Annals of Hepatology, 2013Co-Authors: Joseph E Maakaron, Maria Domenica Cappellini, Giovanna Graziadei, Jad Bou Ayache, Ali T. TaherAbstract:Patients with Thalassemia are often exposed to several risk factors for developing hepatocellular carcinoma (HCC) due to their repeated transfusions. However, even transfusion-independent patients with Thalassemia Intermedia (TI) can develop HCC, which is mainly attributed to a state of iron overload. We report here two cases and review the literature for the association between TI and HCC. Along with our cases, a total of 36 cases of HCC in thalassemic patients were reported in the literature. Of these, 22 (61%) were TI patients with 6 (27%) of them being hepatitis B and C negative. There was no consistency in their characteristics; therefore, we recommended screening thresholds for HCC in TI patients based on their total liver iron concentration (LIC).
Khaled M. Musallam - One of the best experts on this subject based on the ideXlab platform.
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serum ferritin level and morbidity risk in transfusion independent patients with β Thalassemia Intermedia the orient study
Haematologica, 2014Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Mehran Karimi, Giovanna Graziadei, Amal Elbeshlawy, Shahina Daar, Matthew Magestro, Jerome Wulff, Guilhem Pietri, Ali T. TaherAbstract:Similar to other forms of non-transfusion-dependent Thalassemia, the diagnosis of β-Thalassemia Intermedia is associated with a state of iron overload.[1][1]–[3][2] This occurs in the absence of regular transfusion therapy and is primarily attributed to increased intestinal iron absorption
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evaluation of the 5mg g liver iron concentration threshold and its association with morbidity in patients with β Thalassemia Intermedia
Blood Cells Molecules and Diseases, 2013Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Ali T. TaherAbstract:Abstract Iron overload may still occur in transfusion-independent patients with β-Thalassemia Intermedia due to increased intestinal iron absorption. In this study, we evaluated the association between iron overload, using a liver iron concentration threshold of therapeutic significance (≥ 5 mg/g), and morbidity in 168 chelation naive patients with β-Thalassemia Intermedia. We demonstrated that patients with a liver iron concentration ≥ 5 mg/g have a significantly higher prevalence of several serious vascular and endocrine/bone morbidities than do patients with
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evaluation of the 5mg g liver iron concentration threshold and its association with morbidity in patients with β Thalassemia Intermedia
Blood Cells Molecules and Diseases, 2013Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Ali T. TaherAbstract:Iron overload may still occur in transfusion-independent patients with β-Thalassemia Intermedia due to increased intestinal iron absorption. In this study, we evaluated the association between iron overload, using a liver iron concentration threshold of therapeutic significance (≥5mg/g), and morbidity in 168 chelation naive patients with β-Thalassemia Intermedia. We demonstrated that patients with a liver iron concentration ≥5mg/g have a significantly higher prevalence of several serious vascular and endocrine/bone morbidities than do patients with <5mg/g, and we established absolute morbidity risk values differentiating both groups. We also demonstrated that the association between iron overload and morbidity in such patients is independent of the effects of advancing age and disease severity. These findings suggest that treating iron burden in β-Thalassemia Intermedia may be associated with reduction in serious morbidity risk.
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glomerular hyperfiltration and proteinuria in transfusion independent patients with β Thalassemia Intermedia
Nephron Clinical Practice, 2012Co-Authors: Fuad N Ziyadeh, Khaled M. Musallam, Naji S Mallat, Suzanne Koussa, Samir G Mallat, Fadel Jaber, Ali Abdulnabi Mohamed, Ali T. TaherAbstract:Background/Aims: Renal manifestations have been described in β-Thalassemia major and were attributed to transfusional iron overload and chelation therapy. Patients with the milder phenotype, β-Thalassemia Intermedia (TI), remain largely transfusion and iron chelation independent while enduring a chronic hemolytic anemia and primary iron overload. Data on renal function in patients with TI is lacking. Methods: In this cross-sectional study of 50 TI patients, we evaluated the association of estimated glomerular filtration rate (eGFR) and urinary protein to creatinine (UPr/UCr) ratio with relevant patient, disease and laboratory indices. Results: The median age of patients was 28 years (44% males). The eGFR was >90 ml/min/1.73 m2 in all patients, with a median value of 142.3 ml/min/1.73 m2. The median UPr/UCr ratio was 213.2 mg/g. There was a negative correlation between age and eGFR, while the UPr/UCr ratio correlated positively with markers of anemia, hemolysis and iron overload. A total of 24 (48%) patients had evidence of glomerular hyperfiltration, while 7 (14%) had proteinuria (UPr/UCr ratio >500 mg/g). Patients with proteinuria were characterized by elevated liver iron concentration (>7 mg Fe/g dry weight), non-transferrin-bound iron levels and nucleated red blood cell counts. Conclusions: A considerable proportion of TI patients show evidence of abnormally elevated eGFR, with a declining trend towards advancing age. The occurrence of proteinuria is associated with anemia, hemolysis and iron toxicity.
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cerebral infarction in β Thalassemia Intermedia breaking the silence
Thrombosis Research, 2012Co-Authors: Khaled M. Musallam, Ali T. Taher, Mehran Karimi, Eliezer A RachmilewitzAbstract:Despite remarkable advances in understanding cerebrovascular disease attributed to sickle cell anemia, data from other hemoglobinopathies have only recently started to emerge. Several brain magnetic resonance imaging studies confirm a high prevalence of silent ischemic lesions in patients with β-Thalassemia Intermedia, especially in splenectomized adults who are transfusion-independent and those with elevated platelet counts. Large-vessel disease is also common in this patient population but without apparent association with silent white matter infarcts, leaving smaller arteriolar involvement as a potential explanation. The hypothesized pathophysiology is multifactorial with hypercoagulability and toxicity from free iron species playing major roles. The long-term sequelae of such covert findings is unknown, although experience from patients with sickle cell anemia confirms their association with subsequent overt stroke and neurocognitive deficits. The roles of transfusion and antiplatelet therapy to prevent the occurrence and progression of silent ischemic lesions in patients with β-Thalassemia Intermedia should be the focus of future trials.
Mark D. Fleming - One of the best experts on this subject based on the ideXlab platform.
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global loss of tfr2 with concomitant induced iron deficiency greatly ameliorates the phenotype of a murine Thalassemia Intermedia model
American Journal of Hematology, 2021Co-Authors: Paul J. Schmidt, Kevin Fitzgerald, James Butler, Mark D. FlemingAbstract:β-Thalassemias result from mutations in β-globin, causing ineffective erythropoiesis and secondary iron overload due to inappropriately low levels of the iron regulatory hormone hepcidin. Mutations in transferrin receptor 2 (TFR2) lead to hereditary hemochromatosis (HH) as a result of inappropriately increased iron uptake from the diet, also due to improperly regulated hepcidin. TFR2 is also thought to be required for efficient erythropoiesis through its interaction with the erythropoietin receptor in erythroid progenitors. Transmembrane serine protease 6 (TMPRSS6), a membrane serine protease expressed selectively in the liver, participates in regulating hepcidin production in response to iron stores by cleaving hemojuvelin (HJV). We have previously demonstrated that inhibiting TMPRSS6 expression with a hepatocyte-specific siRNA formulation, induces hepcidin, mitigates anemia, and reduces iron overload in murine models of β-Thalassemia Intermedia and HH. Here, we demonstrate that Tmprss6 siRNA treatment of double mutant Tfr2Y245X/Y245X HH Hbbth3/+ thalassemic mice induces hepcidin and diminishes tissue and serum iron levels. Importantly, treated double mutant animals produce more mature red blood cells and have a nearly 50% increase in hemoglobin compared to untreated β-thalassemic mice. Furthermore, we also show that treatment of Tfr2Y245X/Y245X HH mice leads to increased hepcidin expression and reduced total body iron burden. These data indicate that siRNA suppression of Tmprss6, in conjunction with the targeting of TFR2, may be superior to inhibiting Tmprss6 alone in the treatment of the anemia and secondary iron loading in β-Thalassemia Intermedia and may be useful as a method of suppressing the primary iron overload in TFR2-related (type 3) hereditary hemochromatosis.
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RNAi-mediated reduction of hepatic Tmprss6 diminishes anemia and secondary iron overload in a splenectomized mouse model of β-Thalassemia Intermedia.
American journal of hematology, 2018Co-Authors: Paul J. Schmidt, Kaifeng Liu, Gary A. Visner, Kevin Fitzgerald, Shannon Fishman, Tim Racie, Julia Hettinger, James Butler, Mark D. FlemingAbstract:Diminished β-globin synthesis in β-Thalassemia is associated with ineffective erythropoiesis, leading to secondary iron overload caused by inappropriately low levels of hepcidin and to splenomegaly in the symptomatic Thalassemias. Splenectomy is often employed in patients with β-Thalassemia to reduce hemolysis. Expression of the iron regulatory peptide hormone hepcidin is repressed by the serine protease TMPRSS6. Hepcidin induction by RNAi-mediated inhibition of TMPRSS6 expression reduces iron overload and mitigates anemia in murine models of β-Thalassemia Intermedia. To interrogate the efficacy of RNAi-mediated reduction of Tmprss6 in splenectomized β-Thalassemia, splenectomized β-thalassemic Hbbth3/+ animals were treated with a GalNAc-conjugated siRNA targeting Tmprss6 (GalNAc-Tmprss6) and their hematological and iron parameters monitored. We demonstrate that treatment with GalNAc-Tmprss6 significantly diminishes Tmprss6 expression and appropriately elevates hepcidin expression in splenectomized Hbbth3/+ animals. Similar to unsplenectomized animals, treated animals have markedly improved anemia due to diminished ineffective erythropoiesis and reduced iron loading in both serum and tissue. These results suggest that RNAi-mediated reduction of Tmprss6 may have positive outcomes even in splenectomized β-Thalassemia patients.
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combination therapy with a tmprss6 rnai therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of β Thalassemia Intermedia
American Journal of Hematology, 2015Co-Authors: Paul J. Schmidt, Kevin Fitzgerald, Tim Racie, James Butler, Mark Westerman, Mark D. FlemingAbstract:β-Thalassemias result from diminished β-globin synthesis and are associated with ineffective erythropoiesis and secondary iron overload caused by inappropriately low levels of the iron regulatory hormone hepcidin. The serine protease TMPRSS6 attenuates hepcidin production in response to iron stores. Hepcidin induction reduces iron overload and mitigates anemia in murine models of β-Thalassemia Intermedia. To further interrogate the efficacy of an RNAi-therapeutic downregulating Tmprss6, β-thalassemic Hbbth3/+ animals on an iron replete, an iron deficient, or an iron replete diet also containing the iron chelator deferiprone were treated with Tmprss6 siRNA. We demonstrate that the total body iron burden is markedly improved in Hbbth3/+ animals treated with siRNA and chelated with oral deferiprone, representing a significant improvement compared to either compound alone. These data indicate that siRNA suppression of Tmprss6, in conjunction with oral iron chelation therapy, may prove superior for treatment of anemia and secondary iron loading seen in β-Thalassemia Intermedia. Am. J. Hematol. 90:310–313, 2015. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.
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combination therapy with a tmprss6 rnai therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of β Thalassemia Intermedia short title tmprss6 sirna and deferiprone combination therapy in mur
2014Co-Authors: Paul J. Schmidt, Kevin Fitzgerald, Tim Racie, James Butler, Mark Westerman, Mark D. FlemingAbstract:β-Thalassemias result from diminished β-globin synthesis and are associated with ineffective erythropoiesis and secondary iron overload caused by inappropriately low levels of the iron regulatory hormone hepcidin. The serine protease TMPRSS6 attenuates hepcidin production in response to iron stores. Hepcidin induction reduces iron overload and mitigates anemia in murine models of β-Thalassemia Intermedia. To further interrogate the efficacy of an RNAitherapeutic downregulating Tmprss6, β-thalassemic Hbb animals on an iron replete, an iron deficient, or an iron replete diet also containing the iron chelator deferiprone were treated with Tmprss6 siRNA. We demonstrate that the total body iron burden is markedly improved in Hbb animals treated with siRNA and chelated with oral deferiprone, representing a significant improvement compared to either compound alone. These data indicate that siRNA suppression of Tmprss6, in conjunction with oral iron chelation therapy, may prove superior for treatment of anemia and secondary iron loading seen in β-Thalassemia Intermedia. Page 2 of 13 John Wiley & Sons American Journal of Hematology This article is protected by copyright. All rights reserved.
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an rnai therapeutic targeting tmprss6 decreases iron overload in hfe mice and ameliorates anemia and iron overload in murine β Thalassemia Intermedia
Blood, 2013Co-Authors: Paul J. Schmidt, Tim Racie, Julia Hettinger, Anoop K. Sendamarai, Ivanka Toudjarska, David Bumcrot, Stuart Milstein, Brian Bettencourt, Mark D. FlemingAbstract:Mutations in HFE lead to hereditary hemochromatosis (HH) because of inappropriately high iron uptake from the diet resulting from decreased hepatic expression of the iron-regulatory hormone hepcidin. β-Thalassemia is a congenital anemia caused by partial or complete loss of β-globin synthesis causing ineffective erythropoiesis, anemia, decreased hepcidin production, and secondary iron overload. Tmprss6 is postulated to regulate hepcidin production by cleaving Hemojuvelin (Hjv), a key modulator of hepcidin expression, from the hepatocyte surface. On this basis, we hypothesized that treatment of mouse models of HH (Hfe−/−) and β-Thalassemia Intermedia (Hbbth3/+) with Tmprss6 siRNA formulated in lipid nanoparticles (LNPs) that are preferentially taken up by the liver would increase hepcidin expression and lessen the iron loading in both models. In the present study, we demonstrate that LNP-Tmprss6 siRNA treatment of Hfe−/− and Hbbth3/+ mice induces hepcidin and diminishes tissue and serum iron levels. Furthermore, LNP-Tmprss6 siRNA treatment of Hbbth3/+ mice substantially improved the anemia by altering RBC survival and ineffective erythropoiesis. Our results indicate that pharmacologic manipulation of Tmprss6 with RNAi therapeutics isa practical approach to treating iron overload diseases associated with diminished hepcidin expression and may have efficacy in modifying disease-associated morbidities of β-Thalassemia Intermedia.
Mehran Karimi - One of the best experts on this subject based on the ideXlab platform.
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evaluation of endocrine complications in beta Thalassemia Intermedia β ti a cross sectional multicenter study
Endocrine, 2020Co-Authors: Mehran Karimi, Sezaneh Haghpanah, Azita Azarkeivan, Shahina Daar, Tahereh Zarei, Christos Kattamis, Vassilis Ladis, Antonios Kattamis, Yurdanur Kilinc, Saif AlyaarubiAbstract:Data on the prevalence and type of endocrine disorders in β-Thalassemia Intermedia (β-TI) patients are scarce. This multicenter study was designed to determine the prevalence of endocrine complications and the associated risk factors in a large group of β-TI patients. In this cross-sectional multicenter study, 726 β-TI patients, aged 2.5–80 years, registered at 12 thalassemic centers, from nine countries, were enrolled during 2017. In a subgroup of 522 patients (mean age 30.8 ± 12.1; range: 2.5–80 years) from Qatar, Iran, Oman, Cyprus, and Jordan detailed data were available. Overall, the most prevalent complications were osteopenia/osteoporosis (22.3%), hypogonadism (10.1%), and primary hypothyroidism (5.3%). In the subgroup multivariate analysis, older age was a risk factor for osteoporosis (Odds ratio: 7.870, 95% CI: 4.729–13.099, P < 0.001), hypogonadism (Odds ratio: 6.310, 95% CI: 2.944–13.521, P < 0.001), and non-insulin-dependent diabetes mellitus (NIDDM; Odds ratio: 17.67, 95% CI: 2.217–140.968, P = 0.007). Splenectomy was a risk factor for osteoporosis (Odds ratio: 1.736, 95% CI: 1.012–2.977, P = 0.045). Hydroxyurea was identified as a “protective factor” for NIDDM (Odds ratio: 0.259, 95% CI: 0.074–0.902, P = 0.034). To the best of our knowledge, this is the largest cohort of β-TI patients with endocrine disorders evaluated in extremely heterogenic thalassemic populations for age, clinical, hematological, and molecular composition. The study demonstrates that endocrine complications are less common in patients with β-TI compared with β-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in β-TI patients.
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guidelines for diagnosis and management of beta Thalassemia Intermedia
Pediatric Hematology and Oncology, 2014Co-Authors: Mehran Karimi, Naji S Mallat, Nader Cohan, V De Sanctis, Ali T. TaherAbstract:Beta-Thalassemia Intermedia (β-TI) is a genetic variant of beta-Thalassemias with a clinical disorder whose severity falls between Thalassemia minor and Thalassemia major. Different genetic defects are involved in this disorder and, based on severity of disease, clinical complications like skeletal deformities and growth retardation, splenomegaly, extramedullary hematopoiesis, heart failure, and endocrine disorders may be present in untreated patients. Precise diagnosis and management are essential in these patients for prevention of later clinical complications. Diagnosis of TI is based on clinical and laboratory data. There are some treatment strategies like modulation of gamma-globulin chain production with hydroxyurea or other drugs, transfusion, splenectomy, and stem cell transplantation. Iron chelation therapy is also needed in many of these patients even if they are not transfused. The aim of this manuscript is to review the clinical manifestations, complications, genetic defects, and unmet treatments needs in TI.
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serum ferritin level and morbidity risk in transfusion independent patients with β Thalassemia Intermedia the orient study
Haematologica, 2014Co-Authors: Khaled M. Musallam, Maria Domenica Cappellini, Mehran Karimi, Giovanna Graziadei, Amal Elbeshlawy, Shahina Daar, Matthew Magestro, Jerome Wulff, Guilhem Pietri, Ali T. TaherAbstract:Similar to other forms of non-transfusion-dependent Thalassemia, the diagnosis of β-Thalassemia Intermedia is associated with a state of iron overload.[1][1]–[3][2] This occurs in the absence of regular transfusion therapy and is primarily attributed to increased intestinal iron absorption
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frequency and distribution of asymptomatic brain lesions in patients with β Thalassemia Intermedia
Blood, 2012Co-Authors: Mehran Karimi, Sezaneh Haghpanah, Mohammadhadi Bagheri, Mohammadreza Bordbar, Parisa Pishdad, Eliezer A RachmilewitzAbstract:Abstract 5141 We aimed to determine the frequency of asymptomatic brain lesions in a group of patients with β-Thalassemia Intermedia (β-TI) and to evaluate correlation of asymptomatic brain lesions with splenectomy, thrombocytosis, blood transfusions and clinical parameters. Ninety five neurologically intact patients with β-TI were randomly enrolled in this cross-sectional study. Diffusion Weighted Imaging (DWI) brain MRI was performed in every patient to detect cerebral white matter lesions (WML). We found an overall frequency of 15 (15. 8%) for WMLs, 14 (23. 7%) in splenectomized and 1 (2. 8%) in nonsplenectomized patients. The presence of WML was significantly associated with splenectomy (P= 0. 008) and thrombocytosis (P=0. 009). However, after adjustment for splenectomy, thrombocytosis was not significantly associated with the presence of WML (P>0. 05). The number of patients with regular blood transfusions and normal MRI was not significantly higher compared to those with abnormal findings (52. 5% vs 26. 7%; P=0. 092). In untransfused patients, hydroxyurea (HU) administration was associated with a lower incidence of WML (P Disclosures: No relevant conflicts of interest to declare.
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cerebral infarction in β Thalassemia Intermedia breaking the silence
Thrombosis Research, 2012Co-Authors: Khaled M. Musallam, Ali T. Taher, Mehran Karimi, Eliezer A RachmilewitzAbstract:Despite remarkable advances in understanding cerebrovascular disease attributed to sickle cell anemia, data from other hemoglobinopathies have only recently started to emerge. Several brain magnetic resonance imaging studies confirm a high prevalence of silent ischemic lesions in patients with β-Thalassemia Intermedia, especially in splenectomized adults who are transfusion-independent and those with elevated platelet counts. Large-vessel disease is also common in this patient population but without apparent association with silent white matter infarcts, leaving smaller arteriolar involvement as a potential explanation. The hypothesized pathophysiology is multifactorial with hypercoagulability and toxicity from free iron species playing major roles. The long-term sequelae of such covert findings is unknown, although experience from patients with sickle cell anemia confirms their association with subsequent overt stroke and neurocognitive deficits. The roles of transfusion and antiplatelet therapy to prevent the occurrence and progression of silent ischemic lesions in patients with β-Thalassemia Intermedia should be the focus of future trials.