Twenty-nine patients with a positive antimitochondrial antibody titer greater than or equal to 1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1 and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3 and, to a lesser extent, IgG2 was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer greater than or equal to 1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosphatase.

An audit of the effect of anticoagulant prophylaxis in acute exacerbations of severe autoimmune haemolysis was undertaken. All cases of this disorder presenting to one institution over a 16 year period were reviewed. There were 28 patients who had a total of thirty six exacerbations of haemolysis. Anticoagulant prophylaxis had been introduced from 1992 following three cases with fatal pulmonary emboli. Venous thromboembolism occurred in 5 of 15 exacerbations without prophylaxis but in only one of 21 in which prophylaxis was given. It is suggested that auto-immune haemolysis increases the risk of thromboembolism but further studies are required to quantify the risks and to define optimal prophylactic regimens.

No abstract

No abstract

IntroductionThe myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders characterized by ineffective clonal hematopoiesis, acquired genomic instability, and variable risk for transformation to acute leukemia. 1 Most patients with MDS have macrocytic or normocytic anemia, but occasional patients have microcytic red blood cell indices. 2 Rarely, MDS patients with striking hypochromia, microcytosis, and anisopoikilocytosis are found to have acquired hemoglobin H (HbH) disease (␣-thalassemia); this constellation of findings has been called ␣-thalassemia myelodysplastic syndrome (ATMDS). 3 In most patients with ATMDS, a substantial proportion of red blood cells contain HbH inclusions after supravital staining, and severely decreased ␣-globin chain synthesis is paralleled by diminished ␣-globin cytoplasmic and nuclear mRNA levels. 3,4 The common inherited forms of ␣-thalassemia are frequently a consequence of deletions or point mutations affecting the duplicated ␣-globin genes (␣␣/␣␣) on chromosome 16 or, less commonly, deletions of the remote regulatory elements that control ␣-globin expression. 5,6 Germline mutations of ATRX, an X-linked gene encoding a chromatin remodeling protein that regulates the expression of diverse genes, cause mild ␣-thalassemia associated with developmental abnormalities (ATR-X syndrome). 7 ATRX mutations down-regulate the expression of all 4 ␣-globin genes, but the ␣-globin cluster itself is normal.Recently, we have shown that acquired, somatic mutations in the ATRX gene can also underlie ATMDS syndrome. 8,9 To date, 12 unique pathologic ATRX mutations have been found in patients with typical features of ATMDS, including striking "thalassemic" blood pictures, substantial amounts (more than 10%) of HbH, and severely reduced ␣/␤ globin chain biosynthesis ratios. 8,9 However, we have also studied several patients with MDS who have hypochromic, microcytic, red blood cell morphology, but in whom HbH inclusions are only present in a small proportion of erythrocytes or cannot be detected at all. To date, none of these patients have been shown to have mutations in the ATRX gene; the underlying molecular defect remains unknown.Here we report acquired ␣-thalassemia and rare HbH inclusions in an MDS patient. In contrast to previously reported cases of ATMDS, an abnormal hematopoietic clone in this patient had an acquired deletion involving the telomeric region of one allele of chromosome 16, removing 2 of the 4 ␣-genes (ie, genotype ϪϪ/␣␣). This case illustrates a second, less severe mechanism by which ␣-thalassemia may occur as an acquired abnormality in the context of hematologic malignancy. Study designA 72-year-old white British man had microcytic, hypochromic anemia (hemoglobin count, 10.4 g/dL; mean corpuscular volume, 64 fL; mean corpuscular hemoglobin level, 21.7 pg) and neutropenia (leukocyte count, 4.8 ϫ 10 9 /L with 14.7% neutrophils). Two years earlier, he had undergone partial pneumonectomy for localized lung carcinoma; at that time complete blood count finding...