Successful treatment of iron overload with phlebotomies in two siblings with congenital dyserythropoietic anemia--type II (CDA-II).

Successful treatment of iron overload by phlebotomies has been reported in two splenectomized siblings with congenital dyserythropoietic anemia--type II (CDA-II). In both patients 400 ml of blood were withdrawn every month. During three years 12 200 ml of blood were removed. The serum ferritin levels decreased from 1450,4 microg/L and 1131,7 microg/L to 447 microg/L and 457 microg/l, respectively. The transferrin saturation dropped from 0,99 at the start of the therapy to 0,64 and 0,86, respectively. The values of Hb, Hct, erythrocyte counts and MCV did not change as well as did not change reticulocyte counts, reticulocyte index, and RDW. Both patients tolerated repeated phlebotomies well. The decrease of bilirubin and normal values of haptoglobin might be the concequence of diminished destruction of erythrocytes and their precursors. Our observation confirms that phlebotomies can be used with success in CDA patients with mild anemia as treatment modality of iron overload.

Excess of Pappenheimer bodies (siderocytes) in two splenectomized siblings with congenital dyserythropoietic anemia--type II (CDA-II) and iron overload.

In two splenectomized siblings with congenital dyserythropoietic anemia type-II (CDA-II) and iron overload excess of Pappenheimer bodies reaching 46.4% and 15.9% respectively was found. Cause, significance and differential diagnosis of this finding were discussed.

[Congenital dyserythropoietic anemia--type II (CDA-II) in 3 siblings with long-term follow up and iron overload]. / Kongenitální dyserytropoetická anémie-typ II (CDA-II) u trí sourozencu s dlouhodobým sledováním a pretízením zelezem.

The diagnosis of congenital dyserythropioetic anemia-type II (CDA-II) was established in 1974 in three siblings aged 20, 18 and 5 years, respectively. Liver biopsy performed in two elder siblings on admission revealed liver siderosis. Anemia showing haemolytic component with destruction of erythrocytes in the spleen was corrected after splenectomy. Increased number of erythrocytes showing "the double membrane phenomenon" was found in the peripheral blood after splenectomy. All three siblings developed cholecystolithiasis with choledocholithiasis and obstructive jaundice in two of them. Two patients at the age of 49 and 34 years (the third died in an accident at the age of 40 years) developed 29 years after the diagnosis of CDA-II had been established signs of iron overload with transferin saturation 99%, serum ferritin 1450.4 microg/l and 1131.7 microg/l respectively, and hepatic iron concentration (dry weight) 14,843 microg/g and 15,415 microg/g (norm 70-1400 microg/g) respectively. No mutations of HFE gene (C282Y and H63D) were found. Liver biopsy showed heavy accumulation of hemosiderin in hepatocytes and reticuloendothelial cells. The structure of the liver tissue was not changed, only mild fibrosis in portal area was present in the older patient. Because of iron overload therapy with phlebotomy once monthly (400 ml) has been started in both patients. In peripheral blood films excess of Pappenheimer bodies was found.

[Sir William Osler's legacy]. / Odkaz Sira Williama Oslera.

William Osler (1849-1919) is generally regarded as one of the greatest and most respected physicians in the history of medicine. As an outstanding clinician and a professor of medicine at four universities in three countries he exerted a profound influence on medical education. His textbook "The Principles and Practice of Medicine" became the most popular treatise on medicine in the world. He emphasized the value of hard work. His compassion and concern for patients, students and colleagues reflected his personality. Osler's humanism, his philosophy and views did not lose their validity even today.

Imatinib mesylate (STI 571)--a new oral target therapy for chronic myelogenous leukemia (CML).

The publication provides an up-to-date review of the significance of cytogenetic abnormalities in chronic myelogenous leukemia (CML) and the development of a promising agent with specific molecular target against tyrosine kinase, product of the BCR-ABL fusion gene, namely imatinib mesylate (STI 571, Glivec). The publication summarizes the achieved results with this compound in the chronic phase CML (in patients resistant to interferon and in newly diagnosed patients) further in patients in the accelerated phase and in blast crisis and in patients in relapse after allogeneic stem cells transplantations for CML. The results in Ph+ acute lymphoblastic leukemia are also presented. The mechanisms of resistance to imatinib mesylate and the possibilities how to overcome or circumvent it are mentioned (escalation of the dosage, combination of imatinib with some other treatment modalities as immunotherapy, interferon or convention chemotherapy and development of new drugs).

Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation.

Congenital dyserythropoietic anemia type II (CDA II) is the most frequent type of congenital dyserythropoietic anemia. More than 200 cases have been described, but with the exception of a report by the International CDA II Registry, these reports include only small numbers of cases and no data on the lifetime evolution of the disease. Since 1967, we were able to follow 48 cases of CDA II from 43 families for up to 35 years. All patients exhibit chronic anemia of variable severity requiring regular red cell transfusions only in a minority of children; 60% developed gallstones before the age of 30 years, and 16 patients had cholecystectomy between 8 and 34 years of age. Iron overload was a frequent complication. In 16 cases, iron depletion started between 7 and 36 years. Three patients died from secondary hemochromatosis. Splenectomy, performed in 22 cases, led to moderate increases in hemoglobin values and eliminated the need for transfusions but did not prevent further iron loading. The current recommendation is to consider splenectomy if the anemia compromises patients' performance, and to manage iron overload according to the guidelines derived from patients with thalassemia.

[History of paroxysmal nocturnal hemoglobinuria]. / Historie paroxysmální nocní hemoglobinurie.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal somatic stem cell disorder characterized by intravascular hemolysis, hypercoaguability, and bone marrow failure. Hemolysis is attributed to somatic mutations in the PIG-A gene responsible for the formation of the glycosylphosphatidylinositol (GPI) anchor, that binds CD 59 and CD 55 to the membrane surface. Their absence from the red cell leads to hemolysis whenever complement is activated. PIG-A gene mutations are not sufficient per se for the development of PNH. The history of PNH is a fascinating story depicting the development of our knowledge of the disease since the first clinical description by Paul Strübing in 1882 till the elucidation of the hemolysis on the molecular level. The article describe the historical steps of this process. The pathogenesis of PNH has been significantly elucidated in the last years, but many questions remain to be clarified.