Iron Supplementation, Response in Iron-Deficiency Anemia: Analysis of Five Trials.

BACKGROUND: Oral iron-replacement therapy is the mainstay of treatment for iron-deficiency anemia, but it is often poorly tolerated or ineffective. Hemoglobin response at day 14 of oral iron may be useful in assessing whether and when to transition patients from oral to intravenous (IV) iron. METHODS: Pooled data from 5 randomized trials were analyzed to compare oral and IV iron-replacement therapy for iron-deficiency anemia. Treatment criteria and assignment to oral versus IV iron were defined per protocol; this analysis included only subjects receiving oral iron. Responders were subjects with ≥1.0-g/dL increases in hemoglobin at day 14, and nonresponders were those with smaller increases. Demographic and clinical characteristics were evaluated for association with hemoglobin response at multiple timepoints. RESULTS: Most subjects (72.8%) were classified as responders. The proportion of subjects with hemoglobin increases ≥1.0, ≥2.0, and ≥3.0 g/dL was greatest among those with postpartum anemia, intermediate among those with heavy uterine bleeding or gastrointestinal-related causes of anemia, and lowest among those with other causes; this proportion was also significantly greater among responders than nonresponders. A ≥1.0-g/dL increase in hemoglobin on day 14 most accurately predicted satisfactory overall hemoglobin response to oral iron on day 42/56 (sensitivity 90.1%; specificity 79.3%; positive and negative predictive values of 92.9% and 72.7%, respectively). Iron-replacement therapy improved quality of life and reduced fatigue. CONCLUSION: Hemoglobin responses <1.0 g/dL at day 14 of oral iron identify subjects with iron-deficiency anemia who should be transitioned to IV iron supplementation.

Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment courses averaged 168 days. Adjunctive hemostatic therapy with recombinant factor VIIa and prothrombin complex concentrate has been reported, and phenobarbital has been used to expedite LAAR metabolism.

Efficacy and safety of erythropoietin and intravenous iron in perioperative blood management: a systematic review.

The use of erythropoietin (EPO) and intravenous (IV) iron as bloodless therapeutic modalities is being explored in the current era of restrictive transfusion strategies and perioperative blood management. It is unclear, however, whether the evidence in the literature supports their safety and efficacy in reducing perioperative red cell transfusions. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a systematic review to evaluate their use in a variety of perioperative settings. We performed a literature search of English articles published between July 1997 and July 2012 in MEDLINE via PubMed, The Cochrane Library, and CINAHL. Only studies with a comparator group were eligible for inclusion. Twenty-four randomized controlled trials (RCTs) and 15 nonrandomized studies were included in the final review. Using the Cochrane risk of bias tool, 8 RCTs were assessed to be at low risk for methodological bias. Of these, however, only 4 RCTs were adequately powered to detect a reduction in transfusion rates. Patients with preoperative iron deficiency anemia may have an earlier and more robust hemoglobin recovery with preoperative IV iron therapy than with oral iron supplementation. A short preoperative regimen of EPO, or a single dose of EPO plus IV iron in the preoperative or intraoperative period, may significantly reduce transfusion rates (number needed to treat to avoid any transfusion ranged from 3 to 6). With regard to the safety of erythropoietin-stimulating agent therapy, IV iron appears to be as well tolerated as oral iron; however, the incidence of severe anaphylactic-type reactions attributable to IV iron is difficult to estimate in prospective trials because of its relatively infrequent occurrence. Furthermore, EPO may increase the risk of thromboembolism in spinal surgery patients who receive mechanical antithrombotic prophylaxis in the perioperative period so pharmacological thromboprophylaxis is advised. Future low risk of bias, adequately powered prospective efficacy, and safety trials in various surgical settings that traditionally require red cell transfusions would be required to make evidenced-based conclusions about the clinical significance of erythropoietin-stimulating agent as a transfusion avoidance strategy in perioperative blood management.