Role of hematopoietic growth factors in transfusion medicine

Recombinant human growth factors are expected to have a significant impact on the use of allogeneic blood components. For example, recombinant human erythropoietin has had a significant impact on blood transfusion in renal dialysis patients. Likewise, myeloid growth factors have reduced infections and hospital stay by promoting hematologic recovery after high-dose ablative chemotherapy. The high costs of these agents mandate that their use be limited to settings where they are clinically indicated. This review discusses the emerging clinical data to help establish guidelines for the use of hematopoietic growth factors. Comments regarding the myeloid growth factors are restricted to their emerging role in stem cell transplantation, because this clinical setting is anticipated to have the greatest impact in the use of allogeneic blood components in oncology.     

Hematopoietic growth factors for the treatment of myelodysplastic syndromes

Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), rh granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or rh interleukin-3 (rhIL-3) effectively stimulate and expand marrow myelopoiesis resulting in a dose-dependent increment of peripheral blood neutrophils in most patients with myelodysplasias (MDS). Clinical outcome with fewer infections have been reported in a few studies using rhG-CSF or rhGM-CSF, including a large randomized, controlled trial with rhGM-CSF. Clinical effective stimulation of megakaryopoiesis and erythropoiesis are however infrequent. Recently, rh erythropoietin (rhEpo) has been used to overcome the ineffective erythropoiesis in MDS to reduce transfusions needed. However, the efficiency has been low in most studies with marked differences in response rates. The most impressive clinical results were obtained in patients with milder forms of MDS combined with low prestudy endogenous S-Epo levels. The possible synergistic effect of combining rhEpo with rhG-CSF or rhGM-CSF has been studied with erythropoietic response rates of about 40%. The safety of the cytokine administration seems acceptable with no significant stimulation of leukemic myelopoiesis and subsequent progression into overt acute myeloid leukemia. In conclusion, combinations of hematopoietic growth factors may be of clinical benefit in some patients with MDS. However, due to the cost and unpredictable clinical outcome there is a need for extended laboratory research to understand the functional defects of MDS stem cells and progenitors.     

Mathematical calculations in transfusion medicine

This article provides simple mathematical formulas for approximating values such as blood volume, red cell mass, and plasma volume. Additionally, other useful formulas and examples are given to estimate increments in hemoglobin, platelets, and factor VIII levels following the transfusion of blood components.     

Blood groups and transfusion medicine in Taiwan

There are significant differences in the frequencies of various blood group antigens between Taiwanese and Caucasians, and also in the frequencies of the corresponding alloantibodies. The most interesting discoveries concerning Taiwanese are: 1) The most common ABO subgroups are the B3 phenotype, followed by the Ael phenotype. 2) The secretory H-deficient para-Bombay phenotype (OHm), which results from mutations in five different h genes, is not uncommon. 3) The Le(a+b+) phenotype has a frequency of about 25% and the Le(a+b-) phenotype is absent except in a few of the indigenous groups. 4) Anti-'Mi(a)' is the most common clinically significant alloantibody causing intravascular hemolytic transfusion reactions and hemolytic disease of the newborn. 5) The incidence of the corresponding MiIII blood group phenotype varies among the different ethnic groups, ranging from 0% among descendants of mainland Chinese from north of the Yangste to 88.4% among the Ami tribe. 6) There is an almost complete absence of Di(a) and St(a) antigens among the indigenous populations, in contrast to incidences of greater than 2% among the Chinese ethnic groups. 7) Nearly all (99.67%) Taiwanese are positive for the Rh(D) antigen. Among those with Rh(D) negative phenotype, about 30% have a very weak Rh(D) positive phenotype (Del phenotype). Since the corresponding anti-D antibody is also rarely encountered, routine D typing is not necessary. 8) Some rare blood group phenotypes found in Taiwanese are the i phenotype associated with congenital cataract, DVI phenotype, Dc- phenotype, Jk(a-b-) phenotype, and Lu(a-b-) phenotype.     

Current good manufacturing practices for transfusion medicine

Transfusion medicine is most tightly controlled in the US by CGMPs that are written as regulations, guidances, and quality management documents. Because the US regulatory scheme requires that each unit of human blood donated for transfusion (and other purposes) be documented from the moment of donor registration until the last component of that donation is finally disposed of, there is precious little that remains solely within the discretion of the treating physician who orders transfusions for her or his patients. An additional complication for transfusion medicine specialists is that the search for the requirements must extend to all possible areas of information, including the possibly unexpected source within the private sector.     

Concern mounts as transfusion medicine loses its lustre

Transfusion medicine is in trouble. Several factors, ranging from the tainted-blood scandal to changes in the way the system operates, mean that young physicians are avoiding the specialty. Dr. Antonio Giulivi of the Red Cross says the issue is serious because these specialists act as the system's overseers, and this fact won't change when the Red Cross gets out of the blood business in September.     

Implementation of a continuous quality improvement program in transfusion medicine]

The transfusion safety is one of the themes of National Quality Assurance Programme 1995/1996 (National Agency for the Promotion of Medical Evaluation-ANDEM/Direction des H?pitaux (National Hospital Authority)). The Quality Assurance Programme (QAP) in transfusion medicine of our University Hospital has been selected. The QAP is a prospective and normative programme, in which all the actors of the transfusion process are involved. The goals are: i) to assure the quality and the safety of the blood products delivered all along the chain leading to blood or blood components transfusion; ii) the guarantee of the exhaustiveness and the quality of information about the transfusion process that are used to mark out blood products; iii) the standardization of the different steps and the creation of "tools" in order to control the application of written procedures.     

Transforming growth factors and cancer

OBJECTIVE: To study the possible influence of ursodiol (ursodeoxycholic acid), a hydrophilic bile acid, on cyclosporine (CsA) bioavailability. METHODS: Seven adult liver transplant recipients participated in a randomised cross-over pharmacokinetic study comparing ursodiol (600 mg) with placebo in single doses. Blood concentrations of CsA were measured by HPLC. RESULTS: There was no significant effect of ursodiol on CsA absorption: AUC was 5011 vs 5486 ng.h.ml-1, Cmax was 832 vs 871 ng.ml-1 and tmax was 2 vs 2 h, after ursodiol and placebo, respectively. CONCLUSION: Although a significant period effect was observed, we conclude that a single dose of ursodiol has little effect on CsA absorption in liver transplant patients and that an interaction in the intestinal lumen between these two drugs is unlikely.     

Skeletal growth factors

Growth factors are polypeptides with important actions on the replication and differentiated function of cells. Skeletal cells synthesize a variety of growth factors, which are believed to act in an autocrine or paracrine fashion. These growth factors include platelet-derived growth factor, fibroblast growth factor 1 and 2, insulin-like growth factor I and II, transforming growth factors beta 1, 2, and 3, and selected bone morphogenetic proteins. Skeletal cells also synthesize specific binding proteins for selected growth factors. In addition, bone marrow cells synthesize a variety of cytokines known to have important actions in bone remodeling. Fibroblast growth factors and platelet-derived growth factors are, for the most part, mitogenic for skeletal cells, whereas insulin-like growth factors and transforming growth factor beta enhance the differentiated function of the osteoblast. Growth factors also modify osteoclast recruitment and function and as such, bone resorption. Skeletal growth factors can be regulated at the level of synthesis, activation, binding proteins, and receptor binding, and, as a result, their activity can be modified by exogenous agents.     

Evaluation of transfusion practice. Surveys for evaluating the practice of nursing care in transfusion medicine in four hospital sites

In four medical centers, transfusion medicine care practices were evaluated by testing the nursing staff with a list of questions. The anonymous test evaluated the knowledge and transfusion practices, and in one of them the bed-side compatibility control procedure in particular. These tests showed failures in the labeling of tubes during phlebotomy for immuno-hematologic testing, in blood product conservation in the ward, and in bed-side compatibility testing which is not always carried out fully at the bed-side. These results, showed on which topics the teaching program should emphasize so as to improve the quality of blood transfusion in the medical centers according to legal obligations.     

Fibroblast growth factors and their receptors

Fibroblast growth factors (FGFs) represent a group of polypeptide mitogens eliciting a wide variety of responses depending upon the target cell type. The knowledge of the cell surface receptors mediating the effects of FGFs has recently expanded remarkably. The complexity of the FGF family and the FGF-induced responses is reflected in the diversity and redundancy of the FGF receptors. In this review, a number of biochemical characteristics and biological properties of the FGF family and its receptors are described and their expression both in normal tissues and in tumours is discussed. Finally we speculate on the targetting of growth inhibition agents to tumours through FGF receptors.     

Insulin-like growth factors and ovarian physiology

OBJECTIVE: To review the available information regarding the roles of insulin-like growth factor (IGF)-IGF binding protein (IGFBP) system in ovarian physiology. DESIGN: Studies that specifically relate to the roles of ovarian folliculogenesis, oocyte maturation, and ovulation were identified through the literature and Medline searches. RESULTS: Numerous actions of the IGFs have been demonstrated in the ovary, including an enhancement of cell proliferation, aromatase activity, and progesterone biosynthesis. The ovarian IGF system, comprised of IGF-I and IGF-II peptides, IGFBPs and IGF receptors, plays a significant role in the process of follicular development. In addition, IGF-I stimulates the meiotic maturation of follicle-enclosed oocytes in vitro via the IGF-I receptors. IGFBP-3 significantly inhibit gonadotropin-induced ovulation and oocyte maturation by neutralizing endogenously produced IGF-I. Thus, the intraovarian IGF-IGFBP system play a significant role in the processes of follicular development, oocyte maturation, and ovulation. CONCLUSION: IGF-IGFBP systems have autocrine/paracrine regulatory actions in ovarian physiology. The disturbance of the IGF-IGFBP system in human ovaries may lead to an ovulation, disorders of androgen excess, and infertility.