Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support.
Each year in Australia, about 1 in 1000 people develop a first episode of venous thromboembolism (VTE), which approximates to about 20 000 cases. More than half of these episodes occur during or soon after a hospital admission, which makes them potentially preventable. This paper summarises recommendations from the National Health and Medical Research Council's 'Clinical Practice Guideline for the Prevention of Venous Thromboembolism in Patients Admitted to Australian Hospitals' and describes the way these recommendations were developed. The guideline has two aims: to provide advice on VTE prevention to Australian clinicians and to support implementation of effective programmes for VTE prevention in Australian hospitals by offering evidence-based recommendations which local hospital guidelines can be based on. Methods for preventing VTE are pharmacological and/or mechanical, and they require appropriate timing, dosing and duration and also need to be accompanied by good clinical care, such as promoting mobility and hydration whilst in hospital. With some procedures or injuries, the risk of VTE is sufficiently high to require that all patients receive an effective form of prophylaxis unless this is contraindicated; in other clinical settings, the need for prophylaxis requires individual assessment. For optimal VTE prevention, all patients admitted to hospital should have early and formal assessments of: (i) their intrinsic VTE risk and the risks related to their medical conditions; (ii) the added VTE risks resulting from surgery or trauma; (iii) bleeding risks that would contraindicate pharmacological prophylaxis; (iv) any contraindications to mechanical prophylaxis, culminating in (v) a decision about prophylaxis (pharmacological and/or mechanical, or none). The most appropriate form of prophylaxis will depend on the type of surgery, medical condition and patient characteristics. Recommendations for various clinical circumstances are provided as summary tables with relevance to orthopaedic surgical procedures, other types of surgery and medical inpatients. In addition, the tables indicate the grades of supporting evidence for the recommendations (these range from Grade A which can be trusted to guide practice, to Grade D where there is more uncertainty; Good Practice Points are consensus-based expert opinions).
Both p16 and p15, encoded by the genes located on chromosome 9p21, are inhibitors of cyclin-dependent kinases (CDK4/6) and the upstream regulators of Rb function. In hematopoietic malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid, and more particularly from B-lineage malignancies except multiple myeloma (MM). To investigate whether these genes are inactivated by deletions, mutations, and hypermethylation of the 5′ CpG islands, we examined 12 MM patients by Southern hybridization and polymerase chain reaction–single-strand conformation polymorphism (PCR-SSCP) analysis. No deletions nor mutations of the p16 and p15 genes were found. However, hypermethylation was observed in 75% for p16 and 67% for p15 in our group of MM patients. Such high frequencies of involvement of these genes in MM make them hitherto the most common genetic abnormalities in this disease. Concomitant hypermethylation, uncommon thus far in the literature of the study of these genes, is a rather common phenomenon, occurring in 67% of our patient group. Moreover, hypermethylation of p16/p15 was associated with blastic disease and concomitant hypermethylation of both genes may be pathogenetically related to plasmacytoma development. These results indicate that these genes are important in MM pathogenesis. Here we report, for the first time in the literature, the high incidences of p16 and p15 alterations in MM, not by homozygous deletions or mutations, but solely by hypermethylation of the 5′ CpG islands, which may be a specific mechanism in this disease.
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