Endogenous EPO concentrations are low in critically ill patients. The bone marrow of these patients is able to respond to exogenous epoetin alfa, as shown by elevated concentrations of reticulocytes and serum transferrin receptors.

Both major and minor surgery induce a state of hypoferraemia in the presence of adequate iron stores. The degree of this transient form of 'anaemia of chronic disease' is related to the extent of surgery. Iron supplementation in the first weeks after surgery (if iron stores were normal before operation) is ineffective.

Hans Verhoef and colleagues report findings from a randomized trial conducted among Tanzanian children at high risk for malaria. Children in the trial received either daily oral supplementation with either zinc alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. The investigators did not find evidence from this study that zinc or multi-nutrients protected against malaria episodes.

SummaryBackground Sodium iron edetic acid (NaFeEDTA) might be a more bioavailable source of iron than electrolytic iron, when added to maize fl our. We aimed to assess the eff ect, on children's iron status, of consumption of whole maize fl our fortifi ed with iron as NaFeEDTA or electrolytic iron.

AimsErythropoietin (EPO) resistance, an important cause of anaemia in patients with heart and renal failure, is associated with increased mortality. The hypothesis of the present study was that exogenous EPO decreases hepcidin levels and that the decrease in hepcidin levels upon EPO treatment is related to the bone marrow response. Methods and resultsIn the EPOCARES trial, patients with renal failure (glomerular filtration rate 20-70 mL/min), heart failure, and anaemia were randomized to receive 50 IU/kg/week EPO (n ¼ 20) or not (n ¼ 13). Haemoglobin (Hb), hepcidin-25, ferritin, reticulocytes, serum transferrin receptor (sTfR), IL-6, and high-sensitivity C-reactive protein were measured at baseline and during treatment. Hepcidin-25 was measured by weak cation exchange chromatography/ matrix assisted laser desorption ionization time-of-flight mass spectrometry. Baseline hepcidin levels were increased compared with a healthy reference population and were inversely correlated with Hb (r 2 ¼ 0.18, P ¼ 0.02), and positively with ferritin (r 2 ¼ 0.51, P , 0.001), but not with renal function, high-sensitivity C-reactive protein or IL-6. Erythropoietin treatment increased reticulocytes (P , 0.001) and sTfR (P , 0.001), and decreased hepcidin (P , 0.001). Baseline hepcidin levels and the magnitude of the decrease in hepcidin correlated with the increase in reticulocytes (r 2 ¼ 0.23, P ¼ 0.03) and sTfR (r 2 ¼ 0.23, P ¼ 0.03) and also with the Hb response after 6 months (r 2 ¼ 0.49, ConclusionIn this group of patients with combined heart and renal failure and anaemia, increased hepcidin levels were associated with markers of iron load and not with markers of inflammation. The (change in) hepcidin levels predicted early and long-term bone marrow response to exogenous EPO. In our group hepcidin seems to reflect iron load and response to EPO rather than inflammation and EPO resistance.--

The decrease in haemoglobin concentration commonly observed after major surgery is usually corrected by red cell transfusions or oral iron medication. The increased awareness of blood-transmissible diseases has led to the restrictive use of homologous blood and to interest in alternatives for correcting anaemia. We investigated the pathophysiology of postoperative anaemia by studying variables of erythropoiesis, iron metabolism, and inflammation in 48 consecutive patients who underwent total hip replacement. Haemoglobin concentration remained low during 14 days after surgery with only a mild increase in erythropoietin concentration and reticulocyte count. No increase in serum transferrin receptor concentration was observed during the first 2 weeks after surgery. Postoperative serum ferritin increased, whereas serum iron, transferrin and transferrin saturation decreased significantly. There was a marked increase in interleukin-6 and C-reactive protein with maximal values on the 1st and 4th post-operative day, respectively. At 6 weeks after surgery, haemoglobin concentration and variables of iron metabolism were almost at the preoperative level and serum transferrin receptor concentration was significantly increased, indicating increased erythropoietic activity. These changes were preceded by the normalization of interleukin-6 and C-reactive protein levels. Haemoglobin, iron, transferrin, and ferritin concentrations were not influenced by iron therapy during the postoperative period and no differences of erythropoietic and iron variables were observed between transfused and non-transfused patients. In conclusion, post-operative erythropoiesis is associated with an inflammatory effect of surgery on iron metabolism, which can explain, despite a slightly increased production of erythropoietin, the persistence of anaemia and the lack of effect of iron supplementation after surgery.

IntroductionHuman coagulation factor V (FV) is a single-chain glycoprotein that plays an important role in maintaining the hemostatic balance. It circulates in blood as an inactive procoagulant with a M r of 330 kd and a structure consisting of 3 homologous A-type domains and 2 homologous C-type domains connected by a heavily glycosylated B domain in the order A1-A2-B-A3-C1-C2. Proteolytic cleavage by thrombin at R709, R1018, and R1545 (single-letter amino acid codes) results in removal of the B domain and converts the procofactor into the fully active cofactor FVa, which consists of a M r 105-kd heavy chain (A1-A2) and a M r 74-or 71-kd light chain (A3-C1-C2), associated via a single Ca ϩϩ ion. [1][2][3] The difference in molecular weight of the light chain reflects the presence of 2 isoforms of FVa (FVa 1 and FVa 2 ) due to alternative glycosylation of the C2 domain, which leads to different affinities for biologic membranes and subsequent overall procoagulant activity. 4,5 In its active form, FVa forms an essential part of the prothrombinase complex that catalyzes the conversion of prothrombin to thrombin by factor Xa in the presence of calcium and a phospholipid membrane. 1-3 Activated protein C (APC) inactivates FVa through cleavage of the active cofactor at R306, R506, and R679 and requires FV as a cofactor in the APC-mediated inactivation of factor VIIIa (FVIIIa). 6,7 Thus, FV plays an important role in the procoagulant pathway as well as in the protein C anticoagulant pathway. The structure of FV is similar to FVIII (both cofactors share approximately 40% homology in their heavy and light chains) and ceruloplasmin, the copper-binding protein in plasma. 8,9 Recently, the crystal structure of the C2 domain of FV has been established 10 and molecular models for the A and C domains of FV have been proposed. 11,12 The gene for coagulation FV has been mapped to chromosome 1q23 13 and spans more than 80 kilobases (kb). It consists of 25 exons and the messenger RNA (mRNA) encodes a leader peptide of 28 amino acids and a mature protein of 2196 amino acids. Roughly, the heavy chain is encoded by exons 1 to 12 and the light chain by exons 14 to 25. The entire B domain is encoded by exon 13, which contains 2 tandem repeats of 17 amino acids and 31 tandem repeats of 9 amino acids that are absent in the B domain of FVIII. 14,15 Deficiency of FV, or parahemophilia, was first described in 1947 by Owren. 16 It is a rare autosomal recessive bleeding disorder with an estimated frequency of one in one million. The phenotypic expression of FV deficiency is variable; heterozygotes are usually asymptomatic, whereas homozygous patients show mild, moderate, or severe bleeding symptoms. Identifying the molecular basis underlying this disease will help to obtain more insight into the mechanisms involved in this variable clinical expression. The recently published complete nucleotide sequence of the FV gene (GenBank accession number Z99572) has facilitated the molecular characterization underlying FV deficiency and reports have ide...

IntroductionA reliable diagnostic biomarker of iron status is required for severely anemic children living in malarious areas because presumptive treatment with iron may increase their infection risk if they are not iron deficient. Current biomarkers are limited because they are altered by host inflammation. In this study hepcidin concentrations were assessed in severely anemic children living in a highly malarious area of Malawi and evaluated against bone marrow iron in order to determine the usefulness of hepcidin as a point of care test.Methods207 severely anemic children were assessed for levels of hepcidin, ferritin, serum transferrin receptor, erythropoietin, hematological indices, C-reactive protein, interleukin-6, malaria parasites and HIV infection. Deficiency of bone marrow iron stores was graded and erythroblast iron incorporation estimated. Interaction of covariates was assessed by structural-equation-modeling.Results and ConclusionHepcidin was a poor predictor of bone marrow iron deficiency (sensitivity 66.7%; specificity 48.5%), and of iron incorporation (sensitivity 54.2%; specificity 61.8%), and therefore would have limitations as a point of care test in this category of children. As upregulation of hepcidin by inflammation and iron status was blunted by erythropoietin in this population, enhanced iron absorption through the low hepcidin values may increase infection risk. Current recommendations to treat all severely anemic children living in malarious areas with iron should therefore be reconsidered.