- important regulator of the proliferation of committed progenitors (BFU-E and CFU-E). - carbohydrate portion of the molecule do not appear to affect the kinetics, potency, or. - Epoetin alfa has been designated an orphan drug by the United States Food and Drug Administration (FDA) for the treatment of the anemia of prematurity and patients with. - Unfortunately, this misuse of the drug has been implicated in the deaths of several athletes, and it should be discouraged.. - Recombinant forms of several of the growth factors have now been produced, including GM-CSF (Lee et al. - function of a number of the myeloid cell lineages (Figure 54–1). - differentiation, and function of the granulocyte lineage. - The effect of the growth factor on neutrophil recovery is less. - A continuous 24-hour intravenous infusion can be used to produce a steady-state serum concentration of the growth factor.. - Frequent blood counts should be obtained to determine the effectiveness of the treatment. - Iron deficiency can affect metabolism in muscle independently of the effect of anemia on oxygen delivery. - Awareness of the ubiquitous role of iron has stimulated considerable interest in the early and accurate detection of iron. - Although total dietary intake of elemental iron in human beings usually exceeds requirements, the bioavailability of the iron in the diet is limited.. - Over 30% of the weight of ferritin may be iron (4000 atoms of iron per ferritin molecule). - About 80% of the iron in plasma goes to the erythroid marrow to be packaged into new erythrocytes. - The limited physiological losses of iron point to the primary importance of absorption as the determinant of the body's iron content. - These requirements (Table 54–4) must be considered in the context of the amount of dietary iron available for absorption.. - Although the iron content of the diet is obviously important, of greater nutritional significance is the bioavailability of iron in food (Hallberg, 1981). - The prevalence of iron-deficiency anemia depends on the economic status of the population and on the methods used for evaluation. - The recognition of iron deficiency rests on an appreciation of the sequence of events that lead to depletion of iron stores (Hillman and Finch, 1997). - hemoglobin and iron values in infancy and childhood are different because of the more restricted supply of iron in young children (Dallman et al.. - Because of the frequency of iron deficiency in infancy and in the menstruating or pregnant woman, the need for exhaustive. - evaluation of such individuals usually is determined by the severity of the anemia. - The magnitude of the marrow response to iron therapy is proportional to the severity of the anemia (level of erythropoietin stimulation) and the amount of iron delivered to marrow precursors. - If no other explanation can be found, an evaluation of the patient's ability to absorb oral iron should be considered. - It is also essential that the coating of the tablet dissolve rapidly in the stomach. - One of the more popular of these is ascorbic acid. - However, these effects are modified by the severity of the iron-deficiency anemia and by the time of ingestion of iron relative to meals. - The timing of the dose is important.. - The former depends on the severity of the anemia. - Intolerance to oral preparations of iron is primarily a function of the amount of soluble iron in the. - In the evaluation of the child who is thought to have ingested iron, a color test for iron in the gastric contents and an emergency determination of the concentration of iron in plasma can be performed.. - In otherwise healthy individuals, the rate of hemoglobin response is determined by the balance between the severity of the anemia (the level of erythropoietin stimulus) and the delivery of iron to the marrow from iron absorption and iron stores. - This reflects the relative availability of the iron dextran stored in the. - All of the iron is eventually released (Kernoff et al. - reticuloendothelial cells can confuse the clinician who attempts to evaluate the iron status of the patient.. - The methionine synthetase reaction is largely responsible for the control of the recycling of folate cofactors. - See text for explanation and Figure 54–9 for structures of the various folate coenzymes. - The three major portions of the molecule are:. - Deficiency of vitamin B 12 can result from a congenital or acquired defect in any one of the following: (1) inadequate dietary supply. - The utility of measurements of the concentration of vitamin B 12 in plasma to estimate supply available to tissues can be compromised by liver disease and (6) the appearance of abnormal amounts of transcobalamins I and III (Tc I and III) in plasma. - In the normal adult, as much as 90% of the body's stores of vitamin B 12 , from 1 to 10 mg, is in the liver. - Vitamin B 12 is stored as the active coenzyme with a turnover rate of 0.5 to 8 g per day, depending on the size of the body stores (Heyssel et al. - The recommended daily intake of the vitamin in adults is 2.4 g. - The supply of vitamin B 12 available for tissues is directly related to the size of the hepatic storage pool and the amount of vitamin B 12 bound to transcobalamin II (Figure 54–8). - Normal individuals have plasma concentrations of the vitamin ranging from 150 to 660 pM (about 200 to 900 pg/ml). - The sensitivity of the hematopoietic system relates to its high rate of turnover of cells. - identified by examination of the bone marrow and peripheral blood. - The diagnosis of a vitamin B 12 deficiency usually can be made using measurements of the serum vitamin B 12 level and/or serum methylmalonic acid level. - Administration of 1000 g is of value in the performance of the Schilling test. - However, some patients show reductions of the concentration of vitamin B 12 in plasma within 30 days, similar to that seen after. - Dietary deficiency in the strict vegetarian, the predictable malabsorption of vitamin B 12 in patients who have had a gastrectomy, and certain diseases of the small intestine constitute such indications. - The relative ease of treatment with vitamin B 12 should not prevent a full investigation of the etiology of the deficiency. - Full understanding of the etiology of vitamin B 12. - Treatment of the Acutely Ill Patient. - The therapeutic approach depends on the severity of the patient's illness. - determined and the patient reevaluated for an illness that could inhibit the response of the marrow.. - The degree and rate of improvement of neurological signs and symptoms depend on the severity and the duration of the abnormalities. - polyglutamates are the storage and active forms of the vitamin. - Since most absorption occurs in the proximal portion of the small intestine, it is not unusual for folate deficiency to occur when the jejunum is diseased.. - Subsequent studies have shown that the rate of induction of megaloblastic erythropoiesis varies according to the population studied and the dietary background of the individual (Eichner et al. - Such rapid fluctuations tend to detract from the clinical utility of the plasma folate concentration.. - The therapeutic use of folic acid is limited to the prevention and treatment of deficiencies of the vitamin. - As described in detail in the section on vitamin B 12 , treatment of the patient who is acutely ill with megaloblastic anemia should begin with intramuscular injections of both vitamin B 12 and folic acid.. - Folinic acid is the appropriate form of the vitamin for use in chemotherapeutic protocols, including. - The therapeutic response may be monitored by study of the hematopoietic system in a fashion identical to that described for vitamin B 12 . - the reticulocyte index reflects the proliferative state of the marrow. - The next several years should see a further expansion of the use of growth-regulating agents in the. - macromolecules in the subendothelial regions of the injured blood vessel. - An individual with a prolonged aPTT and a normal PT is considered to have a defect in the intrinsic coagulation pathway, because all of the. - components of the aPTT test (except kaolin) are intrinsic to the plasma. - monomers by cleaving fibrinopeptides A (16 amino acid residues) and B (14 amino acid residues) from the amino-terminal ends of the A and B chains, respectively. - Removal of the. - zymogen are homologous to trypsin and contain the active site of the protease. - Antithrombin is a plasma protein that inhibits coagulation factors of the intrinsic and common pathways (see below). - Like heparan sulfate, dermatan sulfate is a component of the cell surface and the extracellular matrix. - prolongation of the aPTT and the thrombin time (i.e., the time required for plasma to clot when exogenous thrombin is added). - These effects are independent of the anticoagulant activity of heparin (Wright et al. - Low- molecular-weight heparins have longer biological half-lives than do standard preparations of the drug.. - The anticoagulant effect of heparin disappears within hours of discontinuation of the drug. - Patients with renal failure may require monitoring with an anti–factor Xa assay because of a prolonged half-life of the drug.. - Lepirudin ( REFLUDAN ) is a recombinant derivative (Leu 1 -Thr 2 -63-desulfohirudin) of hirudin, a direct thrombin inhibitor present in the salivary glands of the medicinal leech. - therefore, daily monitoring of the aPTT is recommended. - Structural Formulas of the Oral Anticoagulants. - The vitamin K epoxide reductase is composed of two proteins in the endoplasmic reticulum: microsomal epoxide reductase and a member of the glutathione S- transferase gene family (Cain et al. - Congenital deficiencies of the procoagulant proteins to these levels cause mild bleeding disorders. - and vitamin K–dependent -carboxylation of the 1,25-dihydroxyvitamin D 3. - Warfarin usually is administered orally, but the drug also can be given intravenously without modification of the dose. - recommended because of the risk of hematoma formation.. - Consequently, antibiotics can cause excessive prolongation of the. - Generally, these factors increase the prolongation of the PT. - Patients must be informed of the signs. - Higher doses may be required if more rapid correction of the INR is necessary. - This overlap allows for adequate depletion of the vitamin K–dependent. - Formerly, the results were reported as a simple ratio of the two PT values. - Efforts to standardize testing between laboratories, begun in the mid-1980s, led to the widespread adoption of the INR system of reporting in the 1990s. - Clearance of t-PA primarily occurs by hepatic metabolism, and the half-life of the protein is 5 to 10 minutes. - Platelets contain two purinergic receptors of the P2Y type. - This is a cyclic peptide inhibitor of the RGD binding site on IIb 3 . - The duration of action of the drug is relatively short, with restoration of
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