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Query: UMLS:C0162316 (iron deficiency anemia)
 3,806 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human hookworm infection is a major cause of gastrointestinal blood loss and iron deficiency anemia, affecting up to one billion people in the developing world. These soil-transmitted helminths cause blood loss during attachment to the intestinal mucosa by lacerating capillaries and ingesting extravasated blood. We have isolated the major anticoagulant used by adult worms to facilitate feeding and exacerbate intestinal blood loss. This 8.7-kDa peptide, named the Ancylostoma caninum anticoagulant peptide (AcAP), was purified by using a combination of ion-exchange chromatography, gel-filtration chromatography, and reverse-phase HPLC. N-terminal sequencing of AcAP reveals no homology to any previously identified anticoagulant or protease inhibitor. Single-stage chromogenic assays reveal that AcAP is a highly potent and specific inhibitor of human coagulation, with an intrinsic K*i for the inhibition of free factor Xa of 323.5 pM. In plasma-based clotting time assays, AcAP was more effective at prolonging the prothrombin time than both recombinant hirudin and tick anticoagulant peptide. These data suggest that AcAP, a specific inhibitor of factor Xa, is one of the most potent naturally occurring anticoagulants described to date.
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PMID:Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa. 759 95

Hookworm infection is a major cause of gastrointestinal blood loss and iron deficiency anemia in the developing world. Recently two major anticoagulant serine protease inhibitors have been identified and cloned from adult Ancylostoma caninum hookworms. One of these, A. caninum anticoagulant peptide 5 (AcAP5), is a potent and specific inhibitor of human coagulation factor Xa. A polyclonal IgG has been purified from rabbits immunized with recombinant AcAP5 using affinity chromatography. Using immunohistochemistry, the polyclonal alpha-rAcAP5 IgG localized to the cephalic or amphidial glands, confirming previous biochemical studies that had identified this secretory gland as the primary source of anticoagulant activity in the adult worm. This polyclonal IgG also neutralized the inhibitory activity of recombinant and native AcAP using a single stage chromogenic assay of coagulation factor Xa activity. In addition, the polyclonal IgG also neutralized the anticoagulant activity of native and recombinant AcAP5 as measured by the activated partial thromboplastin time clotting assay. Importantly, this neutralizing activity is species specific, as the polyclonal IgG failed to neutralize the anticoagulant activity of A. ceylanicum. Taken together, these data suggest that the hookworm anticoagulant AcAP5 represents a viable target for future immunization strategies aimed at inhibiting the ability of the adult hookworm to feed on blood in vivo.
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PMID:Ancylostoma caninum anticoagulant peptide-5: immunolocalization and in vitro neutralization of a major hookworm anti-thrombotic. 1137 44

Bloodfeeding hookworms, which currently infect over a billion people in the developing world, are a leading cause of gastrointestinal hemorrhage and iron deficiency anemia. The major anticoagulant inhibitor of coagulation factor Xa has been identified from the hookworm parasite Ancylostoma ceylanicum using reverse transcription PCR and 3'-rapid amplification of cDNA ends. This is the first anticoagulant cloned from a hookworm species for which humans are recognized permissive hosts. Despite approximately 50% amino acid similarity, A. ceylanicum anticoagulant peptide 1 (AceAP1) is both immunologically and mechanistically distinct from AcAP5, its homologue isolated from the dog hookworm Ancylostoma caninum. Studies using plasma clotting times and single stage chromogenic assays of factor Xa activity have demonstrated that the recombinant AceAP1 protein is substantially less potent than AcAP5 and that soluble whole worm protein extracts of adult A. ceylanicum possess less anticoagulant activity than extracts of A. caninum. These values correlate with previously reported differences in bloodfeeding capabilities between these two species of hookworm, suggesting that factor Xa inhibitory activity is predictive of hookworm bloodfeeding capabilities in vivo. These fundamental differences in the mechanism of action and immunoreactivity of the major anticoagulant virulence factors from related Ancylostoma hookworm species may have significant implications for human vaccine development.
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PMID:Molecular characterization of Ancylostoma inhibitors of coagulation factor Xa. Hookworm anticoagulant activity in vitro predicts parasite bloodfeeding in vivo. 1174 14

We wanted to describe the hematologic manifestations of celiac disease (CD) in childhood. This study included 22 children with CD in whom the disease remained undiagnosed until they had presented with hematological abnormalities, such as anemia, thrombocytopenia, leukopenia or prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Anemia was present alone in 19 (86.3%) patients, and leukopenia coexisted with anemia in 2 (9%) patients. Thrombocytopenia was found alone in 1 (4.5%) patient. Twelve patients had an iron deficiency anemia. Iron deficiency coexisted with zinc and vitamin B(12) deficiency in 3 patients, copper and vitamin B(12) deficiency in two, vitamin B(12) deficiency in two, zinc deficiency in two and one patient had combined iron, zinc, and copper deficiency. Males had significantly lower values of hemoglobin (p < 0.05) and MCV (p < 0.05) compared to the females. In conclusion CD should be included in the differential diagnosis in children who present with anemia, leukopenia, thrombocytopenia or prolonged PT and APTT, especially in geographical areas where the prevalence of the CD is high.
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PMID:Hematologic manifestation of childhood celiac disease. 1515 13

A case is presented of a 26-year-old woman who was referred to the hematology clinic because of her report of a family history of plasminogen activator inhibitor-1 (PAI-1) deficiency. Since menarche, she had suffered from severe menorrhagia, but she had assumed that this was unrelated to her mother's history of repeated life-threatening bleeding. Her menorraghia was evident by using greater than 100 pads per period, bleeding as long as 4 continuous months, and even bleeding through her clothes despite using both tampons and pads. Evaluation with pelvic examination, endometrial biopsy, and pelvic ultrasound was unremarkable. Medroxyprogesterone acetate treatment for her dysfunctional uterine bleeding was unsuccessful. Laboratory evaluation revealed iron deficiency anemia but otherwise normal platelets, bleeding time, prothrombin time, activated partial thromboplastin time, and vonWillebrand's studies. Despite any preconceptions, examination for a fibrinolytic defect ultimately demonstrated a PAI-1 antigen level of 11.4 ng/mL (4.0-43 ng/mL) and PAI-1 activity less than 5 AU/mL (5-37 AU/mL) and clinically supported a diagnosis of a hereditary, qualitative PAI-1 defect. She was treated with aminocaproic acid with return to relatively normal menses. Future treatment should also prevent excessive bleeding during trauma, surgery, or childbirth. Further evaluation of this patient and her family is planned and may help elucidate the important role of PAI-1 in the complicated balance between hemostasis and hemorrhage.
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PMID:Menorrhagia due to a qualitative deficiency of plasminogen activator inhibitor-1: case report and literature review. 1524 91

Hookworm infection is a leading cause of gastrointestinal blood loss and iron deficiency anemia in developing countries. Ancylostoma hookworms secrete potent anticoagulants, which have been shown to target coagulation factors Xa and the factor VIIa/Tissue Factor complex, respectively. The goal of these experiments was to determine the mechanism of action of three recombinant hookworm anticoagulants using in vitro assays. Three hookworm coagulation inhibitors were expressed and purified, along with site directed mutants targeting each of the predicted P1 inhibitory reactive site amino acid residues. Using chromogenic assays, it has been confirmed that Ancylostoma caninum Anticoagulant Peptide 5 (AcAP5) inhibits coagulation factor Xa (fXa) by a canonical, substrate-like mechanism. In contrast, Ancylostoma ceylanicum Anticoagulant Peptide-1 (AceAP1) binds to and inhibits fXa by both active site and non-active site mediated interactions. Data from in vitro studies also demonstrates that AceAP1 inhibits the factor VIIa/Tissue complex (fVIIa/TF) and displays a distinct pattern of fXa binding. Together, these data suggest that the human hookworm A. ceylanicum has evolved a single anticoagulant that targets multiple components of the mammalian coagulation response, effectively mimicking the concerted action of the two related inhibitors from A. caninum. Despite the amino acid sequence similarity, AceAP1 appears to interact with coagulation proteases fXa and fVIIa by a novel mechanism, perhaps explaining its spectrum of inhibitory activity.
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PMID:Ancylostoma ceylanicum anticoagulant peptide-1: role of the predicted reactive site amino acid in mediating inhibition of coagulation factors Xa and VIIa. 1527 61

Hookworms are hematophagous nematodes capable of growth, development and subsistence in living host systems such as humans and other mammals. Approximately one billion, or one in six, people worldwide are infected by hookworms causing gastrointestinal blood loss and iron deficiency anemia. The hematophagous hookworm Ancylostoma caninum produces a family of small, disulfide-linked protein anticoagulants (75-84 amino acid residues). One of these nematode anticoagulant proteins, NAP5, inhibits the amidolytic activity of factor Xa (fXa) with K(i)=43 pM, and is the most potent natural fXa inhibitor identified thus far. The crystal structure of NAP5 bound at the active site of gamma-carboxyglutamic acid domainless factor Xa (des-fXa) has been determined at 3.1 A resolution, which indicates that Asp189 (fXa, S1 subsite) binds to Arg40 (NAP5, P1 site) in a mode similar to that of the BPTI/trypsin interaction. However, the hydroxyl group of Ser39 of NAP5 additionally forms a hydrogen bond (2.5 A) with His57 NE2 of the catalytic triad, replacing the hydrogen bond of Ser195 OG to the latter in the native structure, resulting in an interaction that has not been observed before. Furthermore, the C-terminal extension of NAP5 surprisingly interacts with the fXa exosite of a symmetry-equivalent molecule forming a short intermolecular beta-strand as observed in the structure of the NAPc2/fXa complex. This indicates that NAP5 can bind to fXa at the active site, or the exosite, and to fX at the exosite. However, unlike NAPc2, NAP5 does not inhibit fVIIa of the fVIIa/TF complex.
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PMID:Active and exo-site inhibition of human factor Xa: structure of des-Gla factor Xa inhibited by NAP5, a potent nematode anticoagulant protein from Ancylostoma caninum. 1758 2

The aim of this study is to report how pregnancy alters hematology and clinical chemistry values in rats. Female and male Sprague-Dawley rats were mated; the day of copulation was designated as Day 0. Hematology and clinical chemistry measurements were conducted on Days 7, 14, 17 and 21 in pregnant rats. Measurements were also conducted in non-pregnant rats. Red blood cells (RBC), hemoglobin (Hb), hematocrit (Ht), total protein and albumin decreased on Days 7, 14, 17 and 21; sodium, chloride and glucose decreased on Days 14, 17 and 21; iron decreased on Days 17 and 21; hemoglobin content of reticulocytes (CHr), calcium, inorganic phosphorus and the albumin/globulin ratio decreased on Day 21; and total cholesterol, phospholipid and high-density lipoprotein cholesterol decreased on Day 14 in pregnant rats compared with non-pregnant rats. Reticulocyte increased on Days 7, 14 and 17; mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophil count and rate increased on Days 14, 17 and 21; platelets, fibrinogen, triglyceride and free fatty acid increased on Days 17 and 21; and activated partial thromboplastin time was prolonged on Days 17 and 21 in pregnant rats compared with non-pregnant rats. The decreased RBC, Hb, Ht, CHr and iron in pregnant rats indicated that they suffered from iron deficiency anemia. These data can be used as background information for effective evaluation in reproductive toxicology studies.
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PMID:Time-course changes of hematology and clinical chemistry values in pregnant rats. 1867 Jan 70

Iron-polysaccharide complex have been extensively utilized in the treatment of iron deficiency anemia for parenteral administration. Herein, a novel iron-heparin complexed hollow capsules with nanoscaled wall thickness have been fabricated by means of alternating deposition of ferric ions (III) (Fe+) and heparin (Hep) onto the surface of submicroscaled (488 nm) and microscaled (10.55 microm) polystyrene latex particles via both electrostatic interaction and chemical complexation processes, followed by dissolution of the cores using tetrahydrofuran. Confocal micrographs and atomic force microscopy (AFM) images prove that iron-heparin complexed submicroscaled hollow capsules keep spherical shapes in solution and even after drying. The activated partial thromboplastin time (APTT) assay shows that complexing with ferric ions do not compromise the catalytic capacity of heparin to promote antithrombin III-mediated thrombin inactivation. The anticoagulant activity value of (Fe3+/Hep)8 capsules is evaluated to be about 95.7 U/mg, indicating that approximately 0.55 mg heparin was in 1 mg powder of submicroscaled (Fe3+/Hep)8 hollow capsules. Compared with the same dosage of heparin, iron-heparin complexed hollow capsules display a more prolonged anticoagulant duration than heparin. All these results reveal that such submicroscaled iron-heparin complexed hollow capsules have application potential as an injectable anticoagulant vehicle.
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PMID:Novel hollow microcapsules based on iron-heparin complex multilayers. 1885 87