Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.

BACKGROUND: Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care. METHODS: We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices. DISCUSSION: This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019137282.

Anemia-Induced Bleeding in Patients with Platelet Disorders.

Anemia is not only a consequence of bleeding, but also a modifiable risk factor for bleeding in patients with thrombocytopenia or platelet function defects. In this review we outline the mechanism of anemia-induced bleeding in patients with platelet disorders, which involves a disturbance in normal red blood cell (RBC) rheology and reduced platelet margination to the endothelial surface due to a decrease in RBC mass, leading to impaired primary hemostasis and bleeding. Biologically, anemia reduces the mass of RBCs in the central column of flowing blood through a vessel resulting in fewer platelets coming into contact with the endothelial surface at the periphery of the flowing blood column. Thus, anemia results in impaired primary hemostasis. Von Willebrand factor (vWF) is another component of primary hemostasis and vWF deficiency, especially a deficiency of the highest vWF multimers, can also manifest with bleeding when concomitant anemia occurs. Clinically, patients at greatest risk for anemia-induced bleeding include patients with hematological malignancies in whom anemia and thrombocytopenia occur as a result of the underlying disease or the myelotoxic effects of treatment; patients with renal insufficiency with uremic thrombocytopathy and hypoproliferative anemia; and patients with inherited or acquired bleeding disorders affecting primary hemostasis (eg, Bernard-Soulier syndrome, von Willebrand disease) with chronic blood loss and iron deficiency anemia. Underlying abnormalities of any components of primary hemostasis plus concomitant anemia may result in major bleeding disorders; therefore, correction of remediable abnormalities-most notably, correction of the anemia- would be expected to have important clinical benefit. In this review we discuss how the correction of the anemia may lead to improvement of bleeding outcomes in patients with a primary hemostatic defect, supported by evidence from animal models, clinical trials and clinical experience.

The impact of environmental cadmium exposure on type 2 diabetes risk: a protocol for an overview of systematic reviews.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide epidemic, and while its etiology is polygenic, the role of environmental contaminant exposure in T2DM pathogenesis is of increasing importance. However, the evidence presented in systematic reviews on the relationship between cadmium exposure and T2DM development is inconsistent. This overview aims to assess existing evidence from systematic reviews linking cadmium exposure to T2DM and select metabolic disorders in humans. METHODS: Searches will be conducted in Medline, Embase, Web of Science, GEOBASE, BIOSIS Previews, and Cochrane Database of Systematic Reviews. Two reviewers (J.H and S.T.) will independently complete screening, data abstraction, risk of bias evaluation, and quality assessment. The primary outcome will be the association between cadmium exposure and T2DM prevalence. Secondary outcomes will include prediabetes, obesity, dyslipidemia, hypertension, and non-alcoholic fatty liver disease. We will perform a meta-analysis if two or more studies assess similar populations, utilize analogous methods, have related study designs, and evaluate similar outcomes. DISCUSSION: This overview will assess current evidence from systematic reviews for the association between cadmium exposure and risk of T2DM and other metabolic morbidities. This overview may be helpful for policy-makers and healthcare teams aiming to mitigate T2DM risk in populations at risk of cadmium exposure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125956.