Anemia and its clinical consequences in patients with chronic diseases.
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Biomedical subjects
Publications and source records attributed to Lawrence Tim Goodnough.
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Anemia is a common comorbidity in individuals with rheumatoid arthritis (RA). In fact, anemia of the type characterized by low serum iron concentrations in conjunction with adequate iron stores is frequently associated with RA and has served as a model for anemia of chronic disease. A systematic search of the scientific literature published since January 1966 identified 19 articles that reported findings on either the prevalence of anemia in patients with RA or outcomes for patients with anemia and RA. Ten articles addressed the prevalence of anemia in patients with RA. Estimates of the prevalence of mild anemia ranged between 33% and 60%; however, the 2 studies that examined demographics in patients with RA did not identify subpopulations at particular risk for anemia. Twelve articles assessed the impact of the resolution of anemia on symptoms and quality of life (QOL) in patients with RA. For many of the parameters assessed-including swollen, painful, and tender joints, pain, muscle strength, and energy levels-a positive correlation was observed between improvement of symptoms and the resolution of anemia. In addition, 2 studies reported a significant improvement in QOL scores in patients with RA who experienced a response to treatment for anemia. These results suggest that (1) patients with RA who have anemia are likely to have more severe joint disease and (2) if the anemia is successfully treated, the joint disease will likely respond to treatment as well. Whether improvements in QOL and/or joint symptoms occur with improvement of anemia, independent of other signs of an overall response to RA therapy, remains to be determined.
In addition to its proven benefits in hemophilia, recombinant factor VIIa (rFVIIa), is predicted to be of benefit in other situations characterized by profuse bleeding and impaired thrombin generation, due to its ability to enhance thrombin generation on already activated platelets. This article reviews studies that have described the use of rFVIIa in a variety of clinical settings involving refractory hemorrhage. Ex vivo studies revealed that, at pharmacologic doses, rFVIIa significantly shortened the lag time of thrombin generation, resulting in the formation of more thrombin during the initial coagulation process. Anecdotal clinical reports describe how rFVIIa has been used to resolve serious bleeding in thrombocytopenic patients and a study showed how rFVIIa positively reduced bleeding time in 52% of bleeding wounds in patients with thrombocytopenia. It is concluded that rFVIIa has a potential role in patients with thrombocytopenia and clinical hemorrhage.
Recombinant FVIIa (rFVIIa) has been approved for treatment of bleeding in hemophilia patients with inhibitors. It has also been successfully used in nonhemophilia patients with acquired antibodies against FVIII (acquired hemophilia). Pharmacological doses of rFVIIa have been found to enhance the thrombin generation on already activated platelets and, therefore, may also likely be of benefit in providing hemostasis in other situations characterized by profuse bleeding and impaired thrombin generation, such as patients with thrombocytopenia and in those with functional platelet defects. Additionally, it has been used successfully in a variety of less well-characterized bleeding situations, as well as in patients with impaired liver function. To date, case reports, anecdotal experience, and limited clinical trials describe these uses; data from randomized clinical trials are limited. Because of the recent trends in rFVIIa usage in non-approved settings among physicians from various disciplines, significant concerns about its safety, efficacy, and costs have arisen. Additionally, dosing of rFVIIa for these potentially broad clinical applications is not standardized. Currently, the decision on when and where to use rFVIIa for patients with uncontrolled bleeding continues to be one that must be made by individual physicians, assisted by their hospital pharmacotherapeutics and transfusion committees.
Current risk from transfusion is largely because of noninfectious hazards and defects in the overall process of delivering safe transfusion therapy. Safe transfusion therapy depends on a complex process that requires integration and coordination among multiple hospital services including laboratory medicine, nursing, anesthesia, surgery, clerical support, and transportation. The multidisciplinary hospital transfusion committee has been traditionally charged with oversight of transfusion safety. However, in recent years, this committee may have been neglected in many institutions. Resurgence in hospital oversight of patient safety and transfusion efficacy is an important strategy for change. A new position, the transfusion safety officer (TSO), has been developed in some nations to specifically identify, resolve, and monitor organizational weakness leading to unsafe transfusion practice. New technology is becoming increasingly available to improve the performance of sample labeling and the bedside clerical check. Several technology solutions are in various stages of development and include wireless handheld portable digital assistants, advanced bar coding, radiofrequency identification, and imbedded chip technology. Technology-based solutions for transfusion safety will depend on the larger issue of the technology for patient identification. Devices for transfusion safety hold exciting promise but need to undergo clinical trials to show effectiveness and ease of use. Technology solutions will likely require integration with delivery of pharmaceuticals to be financially acceptable to hospitals.
Preoperative autologous blood donation has served as a model for blood loss anaemia. Studies in these patients, along with clinical trials of i.v. iron and recombinant human erythropoietin (rHuEPO) therapy, have furthered our understanding of the relationship between erythropoietin, iron, and erythropoiesis. With supplemental oral iron, the endogenous erythropoietic response to routine autologous blood donation and to the anaemia of chronic illness has been shown to be modest, but predictable. In more aggressive donation and more severe anaemia, the endogenous erythropoietic response is more substantial, but still predictable. Studies in patients undergoing aggressive phlebotomy whilst receiving rHuEPO demonstrate a wide variation in response to rHuEPO dose. This variability is not related to age or gender and suggests factors such as iron-restricted erythropoiesis may be responsible. Supporting evidence arises from the superior erythropoietic response observed in patients with haemochromatosis. These patients maintain very high serum iron and transferrin saturation levels. In response to serial phlebotomy these patients can mount an endogenous erythropoietin response up to five-times greater than healthy individuals. When treated with rHuEPO, patients with haemochromatosis respond with much greater RBC expansion volumes than patients receiving rHuEPO and iron supplementation. Studies show no difference in the degree of endogenously stimulated erythropoiesis between patients with measurable iron stores and those without. However, when treated with rHuEPO, increased erythropoiesis has been observed in patients with measurable iron stores compared with those without. This suggests that, while oral iron supplementation may be sufficient to keep pace with endogenously stimulated erythropoiesis, it may not be adequate to prevent iron-restricted erythropoiesis during rHuEPO therapy. Some studies have suggested that i.v iron may prevent iron-restricted erythropoiesis during rHuEPO therapy although further research is needed. The availability of better tolerated i.v. iron preparations provides an ideal opportunity to study the value of iron therapy in patients with acute blood loss, particularly those undergoing rHuEPO therapy.
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PURPOSE: In addition to historically important issues of blood inventory and blood safety, the costs of blood transfusion are anticipated to have an increasingly important impact on transfusion practices. To address this, we analyzed costs of blood support given to patients undergoing coronary artery bypass graft (CABG) surgery, along with costs of blood components whose transfusions were identified to be unnecessary. PATIENTS AND METHODS: Blood components transfused as part of a previously reported national, multicenter audit of 30 adult patients each at 18 institutions undergoing primary, elective CABG surgery were reviewed. RESULTS: The range of blood purchase costs among institutions was broad, varying over two-fold. The range of red cell units transfused varied over 10-fold, and the range of total components transfused varied over 40-fold. The number of blood components transfused unnecessarily represented 27% of all blood units transfused, ranging from 7% to 43% among institutions. Inappropriate transfusions accounted for 47%, 32%, and 15% of all platelet, plasma, and red cell units transfused. The mean institutional cost for all blood components transfused per patient was $397 +/- $244. The cost per patient of components transfused inappropriately was 24% of this, or $96 +/- $89 (mean +/- SD). CONCLUSION: These costs could be reduced with practice guidelines and quality improvement programs aimed at reducing the number of inappropriate transfusions.