Abnormal uterine bleeding and chronic iron deficiency.

When IDA or ID is suspected, 16 17 a complete blood count (with RBC indices and peripheral smear evaluation) and ferritin levels should be requested ( Chart 3 ). 18 Source: Adapted from Elstrott et al. (2020) 18 Other measurements, such as serum iron, transferrin, and transferrin saturation, are not mandatory. Patients with IDA have low serum iron, high transferrin, and low transferrin saturation. 12 13 Reticulocyte hemoglobin (Ret-Hb) is a good indicator of the amount of available iron, and its dosage does not interfere with inflammatory processes. 19 According to the diagnostic standards of the World Health Organization, IDA is mild to moderate if Hb is between 7 and 12 g/dL, and severe, if Hb is less than 7 g/dL, with small variations according to age, sex or presence of pregnancy. 20 For the adult female population, Hb values below 12 g/dL are considered as anemia and for men, Hb values below 13 g/dL. 20 21 Although Hb is widely used for the evaluation of IDA, it has low specificity and sensitivity, and a biomarker of iron status, such as serum ferritin, should be requested together. 21 Serum ferritin concentration is the most reliable marker of iron storage in the body. Normal values range from 30 to 200 ng/mL (mcg/L), and there is no clinical situation in which low rates do not mean ID. As long as patients with IDA do not have infection or associated inflammatory disease, the cutoff value of 30 ng/mL gives better diagnostic efficiency, with sensitivity of 92% and specificity of 98%. As ferritin is an acute-phase reactor with increased levels in inflammatory, infectious, malignant, or liver diseases, falsely elevated ferritin may be found in the presence of these diseases and IDA. The effect of inflammation on ferritin is to increase it threefold. Therefore, in these patients, the golden rule is to divide the ferritin value by 3, and values less than or equal to 20 ng/mL suggest concomitant IDA. 22

Abnormal uterine bleeding (AUB) in menacme is the leading cause of iron deficiency anemia (IDA) and iron deficiency (ID). All patients with AUB should be investigated and treated. Anemia is one of the most common problems in clinical practice that affects millions of people worldwide. Non-pregnant women account for 30% of all anemia cases in the world, and approximately 60% of them have ID. Oral iron replacement is the most widespread, especially in cases of milder IDA and ID. Intravenous (IV) formulations have gained more space in prescriptions as their safety and efficacy have become more evident.

The main treatments for IDA and ID are iron replacement, correction of nutritional aspects and treatment of AUB. The goal of iron replacement is to provide enough iron to normalize Hb concentrations and replenish iron storage, thereby improving quality of life and symptoms. 13 Regardless of the presence of symptoms, all patients with IDA and most of those with ID without anemia should be treated. 23 24 There are two distinct approaches: prevention strategies targeting populations at risk, such as patients with AUB, and active iron supplementation approaches in confirmed IDA. 13

Intravenous formulations have gained more space in prescriptions as the safety of their use has become more evident. Infusion reactions are rare, usually mild, and if they occur, drug administration can continue at a slower infusion rate. The various injectable formulations have the same efficacy and are especially useful in cases of more vigorous replacement, patients intolerant to oral administration or with malabsorptive processes (for example: patients with inflammatory bowel diseases) and chronic renal patients. Contraindications to use of IV iron are: anemia unrelated to ID, transferrin saturation > 45%, ferritin > 500 ng/mL, active infection/septicemia, severe dysfunction (hepatic or cardiac), pregnant women in the first trimester of pregnancy. Chart 5 shows the IV iron formulations available in Brazil and the main information for the use of these drugs. calculation of iron need: total iron deficiency (mg) = [weight (kg) x DHb (g/dl) x 2.4] + iron reserves (mg)

Although AUB is a very common condition, it should be valued and properly investigated, as it can significantly worsen a woman’s quality of life. According to the etiology, AUB can be effectively treated by quite effective pharmacological and surgical measures depending on age, reproductive desire and other associated conditions. Abnormal uterine bleeding in menacme is the main cause of IDA and ID. The tests requested for diagnosis must include, at least, the blood count, ferritin and iron profile. Iron replacement should be prescribed for these patients, and treatment monitoring is usually performed between 30 and 60 days, depending on the clinical picture. National Commission Specialized in Venous Thromboembolism and Hemorrhage in Women of the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) President: Venina Isabel Poco Viana Leme de Barros Vice-president: André Luiz Malavasi Longo de Oliveira Secretary: Paulo Francisco Ramos Margarido Members: Ana Maria Kondo Igai Cristiano Caetano Salazar Dênis José Nascimento Eduardo Zlotnik Egle Cristina Couto Eliane Azeka Hase Fernanda Andrade Orsi Joaquim Luiz de Castro Moreira Marcelo Melzer Teruchkin Marcos Arêas Marques Mônica Cristina da Costa Drago Souza Valeria Doria Mendes da Costa

The International Federation of Gynecology and Obstetrics (FIGO) classifies the causes of non-pregnancy-related AUB under the PALM-COEIN acronym, referring to Polyps, Adenomyosis, Leiomyoma, Malignancy and hyperplasia, Coagulopathy, Ovulatory dysfunction, Endometrial disorders, Iatrogenic and Not otherwise classified. In general terms, the first group (“PALM”) refers to structural causes (mostly identifiable by imaging exams or histopathology), and the other group (“COEIN”) refers to non-structural causes. The term “dysfunctional uterine bleeding” (DUB), in turn, refers to causes related to hemostasis (“C”), ovulatory dysfunction (“O”) and endometrial primary disorders (“E”), according to the current FIGO classification system. 3

Management of patients with AUB includes assessment of hemodynamic instability and anemia, identification of the source of bleeding, and exclusion of pregnancy. Initially, it is important to determine whether it is acute or non-acute bleeding. The etiological diagnosis will guide therapy and treatment success. 4 5 However, in situations of acute and severe bleeding, treatment can be instituted to stop acute bleeding, followed by investigation. Although the uterus is often the source of abnormal bleeding, any part of the female genital tract (vulva, vagina) may have externalized vaginal bleeding, and this differential diagnosis is necessary. Initial physical examination may reveal vulvar or cervical lesions, guiding specific therapy. Anamnesis focused on the bleeding pattern, the use of medications and the association of other characteristics, signs and symptoms can guide the investigation, leading to the most likely etiologies ( Chart 2 ).

Many physicians are reluctant to use IV iron because of concerns about anaphylaxis. True allergic reactions are extremely rare and overrated. In individuals with asthma, inflammatory rheumatic diseases, or multiple drug allergies, premedication with a glucocorticoid alone is generally recommended.

One of the most common gynecological complaints worldwide is the occurrence of abnormal uterine bleeding (AUB), a term that refers to abnormalities in the amount, duration or frequency of bleeding from the uterus. With a prevalence of 10-30% among women of reproductive age, it can negatively affect the quality of life and is associated with financial losses, reduced productivity, inadequate health status and greater use of health services. 1 2

It is recommended to increase the intake of meat, the main source of heme iron; it is estimated that 100 g of meat corresponds to 1 kg of beans (non-heme iron). Concomitant consumption of fruit juice with vitamin C enhances the absorption of iron from the diet, and the use of an iron pan to prepare meals is also part of the guidelines. It is recommended not to mix milk and tea at the same meal and avoid whole grain cereals and chocolate as a dessert during the period of treatment with ferrous salt. These recommendations are not necessary when ferric salts are used in the treatment, because in these compounds, iron is chelated with sugar or amino acids, and there is no interaction of its absorption with food in general. Foods rich in ascorbic acid (cashew, legumes, guava) and meats in general, favor the absorption of non-heme iron, while phytates, phosphates and carbonates (pineapple, vegetables, milk), tannin (tea, coffee), phosphoprotein (yolk eggs) and drugs that raise gastric pH (antacids, proton pump inhibitors, histamine H2 blockers) make absorption of non-heme iron difficult. Although intestinal iron absorption can increase significantly when iron is deficient (from less than 1% to more than 50% of the iron present in the diet), dietary correction alone is not usually sufficient to treat patients with IDA. 13 16

Abnormal uterine bleeding is a very frequent complaint that negatively affects the quality of life since menacme. Investigation for IDA and ID is mandatory in these patients. The approach to patients with AUB prioritizes stabilization in acute cases, using mainly hormones and antifibrinolytics to stop bleeding. Etiological investigation will guide the therapy in non-acute cases. Treatment selection for ID is driven by several factors, including the presence of inflammation, the time available for iron replacement and the anticipated risk of side effects or intolerance. The treatment of choice for ID is preferably via oral (VO). The increase in hepcidin by oral iron supplements limits oral absorption when large amounts of iron need to be administered or in the presence of inflammatory conditions. Intravenous iron preparations are indicated for the treatment of ID when oral medications are ineffective or cannot be used. They have applicability in a wide range of clinical settings, including chronic inflammatory conditions, perioperative situations, and disorders associated with chronic blood loss. Serious adverse events that occur with IV iron are very rare and well-studied, which provides a basis for educating and preparing staff and patients on how iron infusions can be safely and effectively administered.