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Hermann Heimpel,
Andreas Matuschek,
Momin Ahmed,
Brigitte Bader-Meunier,
Adriana Colita,
Jean Delaunay,
Loic Garcon,
Florinda Gilsanz, Jeroen Goede,
Josef Högel, [......],
Rosi Leichtle,
Juan Munoz,
Silverio Perrotta,
Carlo Piscopo,
Raffaele Renella,
Klaus Schwarz,
Gabriela Smolenska-Sym,
Sunitha Wickramasinghe,
Alberto Zanella,
Achille Iolascon
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ABSTRACT: Congenital dyserythropoietic anemias (CDAs) are rare hereditary disorders characterized by ineffective erythropoiesis and striking abnormalities of erythroblast morphology. The mutated genes are known for the most frequent types, CDA I and II, but data about their frequency do not exist. The objective of this retrospective study was to estimate the frequency of CDA I and II, based on all cases reported in the last 42 yr in publications and identified registries or surveys. Reports were collected of 124 and 377 confirmed cases of CDA I and CDA II cases, respectively. The cumulated incidence of both types combined varied widely between European regions, with minimal values of 0.08 cases/million in Scandinavia and 2.60 cases/million in Italy. CDA II is more frequent than CDA I, with an overall ratio of approximately 3.2, but the ratio also varied between different regions. The most likely explanations for the differences are both differences in the availability of advanced diagnostic procedures and different levels of the awareness for the diagnosis of the CDAs. The estimations reported here are most probably below the true incidence rates, because of failure to make the correct diagnosis and to underreporting. Limited data do not suggest differing levels of risk in identified ethnic groups.
European Journal Of Haematology 07/2010; 85(1):20-5. · 2.61 Impact Factor
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ABSTRACT: Hyperlipidemic myeloma is a rare and poorly understood variant of multiple myeloma. We report the case of a 53-year-old woman with hyperlipidemic myeloma, skin xanthomas and hyperviscosity syndrome who underwent allogeneic bone marrow transplantation. A comprehensive literature search identified 52 additional cases with plasma cell disease and hyperlipidemia. A detailed analysis revealed several characteristics of these patients as compared to multiple myeloma with normal lipid status: (1) IgA paraprotein was present in the majority (53% vs. 21% in classical multiple myeloma). (2) Skin xanthomas, especially in the palmar creases, elbows, and knees were common (70%). (3) Hyperviscosity syndrome occurred more often (26% vs. 2-6%). While conventional lipid-lowering therapy had only marginal effects, successful anti-myeloma therapy also reduced hyperlipidemia. Analyses of the mechanisms leading to hyperlipidemia documented complexes of paraprotein and lipoprotein in 75% of the 32 cases tested, suggesting an inhibitory role of the paraprotein on lipid degradation. In conclusion, the clinical characteristics, the therapeutic options, and the pathophysiologic mechanisms of hyperlipidemic myeloma are comprehensively reported using the available data from all 53 published cases in the literature.
Annals of Hematology 11/2009; 89(6):569-77. · 2.62 Impact Factor
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Felicitas S Boretti,
Paul W Buehler,
Felice D'Agnillo,
Katharina Kluge,
Tony Glaus,
Omer I Butt,
Yiping Jia, Jeroen Goede,
Claudia P Pereira,
Marco Maggiorini,
Gabriele Schoedon,
Abdu I Alayash,
Dominik J Schaer
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ABSTRACT: Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hb-induced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO- and O2-binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.
The Journal of clinical investigation 09/2009; 119(8):2271-80. · 15.39 Impact Factor
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Annals of Hematology 08/2009; 89(2):211-2. · 2.62 Impact Factor
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British Journal of Haematology 05/2009; 146(4):346. · 4.94 Impact Factor
