Vassilios Perifanis

MRI assessment of liver iron content in thalassamic patients with three different protocols: comparisons and correlations

Our aim was to assess liver iron content, in thalassaemic patients, by using three different MR protocols and compare their data. Ninety‐four thalassaemic patients (44 M and 50 F, mean age 25.82 ± 8.3 yrs), were enrolled in the study. In each patient, three measurements of the liver iron content were performed, with the use of a single imager, equipped with a 1.5 Tesla magnet. Liver R2* was measured on gradient‐echo sequence. Calculation of MR‐HIC values was based on an algorithm using liver to muscle (L/M) ratios in five axial gradient‐echo sequences. Finally, determination of liver R2 employed a 16‐echo, spin‐echo pulse sequence. Additionally, myocardial R2* value was determined for each patient. Results showed that all three magnetic resonance imaging (MRI) methods were highly correlated to each other and significantly correlated to serum ferritin concentrations. Liver R2 method showed an increased sensitivity in detecting liver iron contents in the upper range. No correlation occurred between each liver MRI parameter and myocardial R2* values. Finally, we managed to provide formulae for equating values obtaining with any of these three MRI methods.

Treatment of congenital fibrinogen deficiency: overview and recent findings

Afibrinogenemia is a rare bleeding disorder with an estimated prevalence of 1:1,000,000. It is an autosomal recessive disease resulting from mutations in any of the 3 genes that encode the 3 polypeptide chains of fibrinogen and are located on the long arm of chromosome 4. Spontaneous bleeding, bleeding after minor trauma and excessive bleeding during interventional procedures are the principal manifestations. We review the management of afibrinogenemia. Replacement therapy is the mainstay of treatment of bleeding episodes in these patients and plasma-derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments that should be used only when fibrinogen concentrate is not available. Secondary prophylactic treatment may be considered after life-threatening bleeding whereas primary prophylactic treatment is not currently recommended. We also discuss alternative treatment options and the management of surgery, pregnancy and thrombosis in these patients. The development of new tests to identify higher risk patients and of safer replacement therapy will improve the management of afibrinogenemia in the future.

Comparison of effects of different long-term iron-chelation regimens on myocardial and hepatic iron concentrations assessed with T2* magnetic resonance imaging in patients with β-thalassemia major

The aim of this study was to compare the effect of different long-term chelation regimens on heart and liver iron stores with the use of T2* magnetic resonance imaging (MRI) in patients with transfusion-dependent β-thalassemia major. Sixty-four patients (28 men, 36 women; mean age, 26.49 ± 5.8 years) were enrolled in the study. The 3 groups were based on the chelation therapy received. The first group (19 patients) received deferiprone (DFP) (75 mg/kg per day orally), the second group (23 patients) received deferoxamine (DFO) (30–50 mg/kg per day subcutaneously at least 5 times/week), and the third group (22 patients) received a combination of DFO (30–50 mg/kg per day, 2–3 days/week) and DFP (75 mg/kg per day, 7 days/week). MRI scans were acquired with an imager equipped with a 1.5 T magnet, and the data included myocardial and hepatic iron measurements obtained by means of T2*, and ventricular volumes and ejection fractions obtained with standard cardiovascular MRI techniques. The results revealed that the DFP and the combined groups had significantly less myocardial iron than the DFO group (mean myocardial T2*, 35.77 ± 18.3 milliseconds and 38.05 ± 15.3 milliseconds versus 23.77 ± 13 milliseconds [P =.02, andP =.001], respectively). On the contrary, the DFP group had a significantly higher hepatic iron content than the DFO and combined groups (mean hepatic T2*, 3.29 ± 2.5 milliseconds versus 8.16 ± 8.4 milliseconds and 11.3 ±10.9 milliseconds [P =.014, andP =.003], respectively). No correlation was observed between myocardial T2* and hepatic T2* values (r =-0.043;P =.37). Myocardial T2* values were inversely correlated with age (r =-0.249;P =.024) and positively correlated with both left and right ventricular ejection fractions (r = 0.33 [P =.004], andr = 0.279 [P =.014], respectively). Finally, liver T2* was strongly and inversely correlated with serum ferritin concentration (r =-0.465;P =.001). In conclusion, combined chelation therapy seems to sum the beneficial effects of DFO and DFP with respect to hepatic and myocardial iron. Because myocardial iron is not related to measurements of serum ferritin or hepatic T2*, important decisions on clinical management relating to cardiac risk should not rely on these conventional parameters. Thus, the use of MRI for assessing myocardial iron should be adopted in the routine clinical management of patients with β-thalassemia major.

Peripheral blood haematopoietic progenitor cells in patients with beta thalassaemia major receiving desferrioxamine or deferiprone as chelation therapy.

Objectives: The main adverse effect of deferiprone is the development of neutropenia, which occurs via an unknown mechanism. We aimed to gain insight into the pathogenesis of deferiprone‐induced neutropenia by assessing the peripheral blood haematopoietic progenitor cells. Methods: Sixteen patients with beta thalassaemia were studied; nine (Group A) were receiving desferrioxamine and seven (Group B) deferiprone. Ten healthy individuals comprised the control group (Group C). Results: Granulocyte‐erythrocyte‐monocyte‐megakaryocyte colony forming units were significantly more in Groups A and B compared with Group C. Granulocyte‐macrophage colony forming units (CFU‐GM) were significantly more in Group B compared with Group C. Macrophage colony forming units were significantly less in Group B compared with Group C. Granulocyte colony forming units (CFU‐G) were significantly more in Group A compared with Group C. We found a trend in the difference in the number of CFU‐G between patients’ groups (P = 0.123). Adding serum from patients receiving deferiprone to cultures of controls resulted in a maturation arrest of the granulocytic lineage. Conclusion: Our findings point to a maturation arrest at the level of CFU‐GM as a potential mechanism of deferiprone‐induced neutropenia.

Combined chelation therapy improves glucose metabolism in patients with β-thalassaemia major

Douek, D.C., Vescio, R.A., Betts, M.R., Brenchley, J.M., Hill, B.J., Zhang, L., Berenson, J.R., Collins, R.H. & Koup, R.A. (2000) Assessment of thymic output in adults after haematopoietic stemcell transplantation and prediction of T-cell reconstitution. The Lancet, 355, 1875–1881. Hakim, F.T. & Gress, R. (2005) Reconstitution of the lymphocyte compartment after lymphocyte depletion: a key issue in clinical immunology. European Journal of Immunology, 35, 3099–3102. Hakim, F.T., Memon, S., Cepeda, R., Jones, E.C., Chow, C.K., KastenSportes, C., Odom, J., Vance, B.A., Christensen, B.L., Mackall, C.L. & Gress, R.E. (2005) Age-dependent incidence, time course, and consequences of thymic renewal in adults. Journal of Clinical Investigation, 115, 930–939. Mansky, P., Arai, A., Stratton, P., Bernstein, D., Long, L.L., Reynolds, J., Chen, D., Steinberg, S.M., Lavende, N., Hoffman, K., Nathan, P.C., Parks, R., Augustine, E., Chaudhry, U., Derdak, J., Wiener, L., Gerber, L. & Mackall, C. (2006) Treatment late effects in long-term survivors of pediatric sarcomas. Pediatric Blood Cancer, (Epub ahead of print, 26 April 2006). Watanabe, N., De Rosa, S., Cmelak, A., Hoppe, R., Herzenberg, L.A. & Roederer, M. (1997) Long-term depletion of naı̈ve T cells in patients treated for Hodgkin’s disease. Blood, 90, 3662–3672. Weinberg, K., Blazar, B.R., Wagner, J.E., Agura, E., Hill, B.J., Smogorzewska, M., Koup, R.A., Betts, M.R., Collins, R.H. & Douek, D.C. (2001) Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood, 97, 1458–1466.

Poor correlations between measurements of bone quality by quantitative ultrasound sonography and dual energy X‐ray absorptiometry in patients with β‐thalassaemia major

Objectives:  Osteopenia/osteoporosis is a major component of morbidity even in young patients with β‐thalassaemia major. Dual energy X‐ray absorptiometry (DXA) is the reference method for determining bone mineral density (BMD). Quantitative ultrasound sonography (QUS) for bone measurement is a relatively new, inexpensive and radiation‐free method that could serve as an alternative to DXA. Our aim was to assess bone status in thalassaemic patients both with QUS and DXA and, consequently, to investigate the degree of correlation between the two methods.

Management of acute bleeding in a patient with congenital afibrinogenaemia

Summary.  Congenital afibrinogenaemia is a rare bleeding disorder characterized by absence of fibrinogen and varying bleeding tendency. Treatment with fibrinogen concentrates is considered to be the best choice for afibrinogenaemic patients who experience bleeding. We report the case of a 22‐year‐old Greek patient who presented with large muscular haematomas and was treated with fibrinogen concentrates. The efficacy of this treatment and the problems that arose during his hospitalization are being discussed.

Evaluation of Iron Overload in β‐Thalassemia Patients Using Magnetic Resonance Imaging

In response to the excellent work presented by Galia et al. (1), we would like to briefly report our own experience on the use of magnetic resonance imaging (MRI) in the evaluation of iron overload in b-thalassemia (thal). Excessive iron absorption and transfusional overload lead to various organ iron deposits in thalassemic patients, principally affecting the heart, liver and endocrine grands. Heart failure remains the most common cause of death in thalassemic patients, with a reported incidence that reaches a percentage of 50% before age 35 in certain areas (2). This complication may be reversible, provided heart siderosis is promptly detected and intense chelation therapy is instituted in time. Quantitative studies of iron balance have been limited by the lack of a ‘‘gold standard’’ method. Serum ferritin and urinary iron excretion are qualitative indexes, influenced by factors such as infection, inflammation and liver disease (3). Hepatic biopsy provides the most quantitative measuring means but involves discomfort and relative risks, while biomagnetic susceptometry, a non invasive, well-calibrated and validated method, has limited clinical value due to its high cost and required technical demands. Magnetic resonance imaging has been considered a promising non invasive modality, as the tissue iron deposits causes a reduction in T2 relaxation time, thus decreasing the relevant signal density. Investigators have used various techniques,

Hemophagocytic Syndrome Associated with Multiple Myeloma

Hemophagocytic syndrome (HPS) is an uncommon reactive disorder characterized by proliferation of histiocytes that actively engulf other hematopoietic cells causing cytopenia. It complicates several diseases including hematological neoplasias. We report the case of a 54-year-old woman who was admitted to our hospital with fever of unknown origin. Her clinical picture was characterized by renal failure, splenomegaly and pancytopenia. Findings on bone marrow examination showed HPS associated with multiple myeloma. A review of the literature revealed that only one case has previously been published.

Elevated Levels of Serum Vascular Endothelial Growth Factor in Patients with Polycythaemia vera

Angiogenesis seems to be a prominent event of myeloproliferative diseases. There are few reported data on angiogenesis and the significance of its stimulator, the vascular endothelial growth factor (VEGF), in polycythaemia vera (PV). We report our observation of elevated serum VEGF levels in patients suffering from PV. Twenty patients with PV and 20 age-matched healthy subjects were enrolled. VEGF levels were measured by a quantitative sandwich enzyme immunoassay. Serum VEGF levels in PV were found to be very significantly higher than in healthy individuals (569.7 ± 101.2 vs. 164.7 ± 32.8 pg/ml, p = 0.001). We found no correlation between VEGF and haemoglobin, platelet or leucocyte counts in the patient group. Different therapeutic regimens had no influence on VEGF levels. However, in the control group, we observed a positive correlation between VEGF levels and platelet counts (r = 0.52, p = 0.02). Platelet counts did not differ between patients and healthy subjects. We also evaluated platelet-poor plasma VEGF levels in 10 patients and in all healthy individuals. We found very low levels of VEGF, approximately zero in most cases, in both groups and there was obviously no difference between the two groups. Our results indicate that VEGF is overproduced in PV. However, follow-up studies are needed to verify the role of this factor.