Железодефицитные новости

[Dr.Vad]

Рабепразол-индуцированная ЖДА, которая не поддается лечению пероральным железом, но откорректировалась за 3 мес. при смене на фамотидин:

Intern Med. 2014;53(20):2297-9.
Iron-deficiency Anemia Caused by a Proton Pump Inhibitor.

[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

Две публикации из Португалии о том, что и в детском возрасте причиной рефрактерной ЖДА может быть аутоиммунный атрофический гастрит:

Autoimmune gastritis presenting as iron deficiency anemia in childhood.
Gonçalves C, Oliveira ME, Palha AM, Ferrão A, Morais A, Lopes AI.
World J Gastroenterol. 2014 Nov 14;20(42):15780-6.
[Ссылки доступны только зарегистрированным пользователям ]

Refractory iron-deficiency anemia and autoimmune atrophic gastritis in pediatric age group: analysis of 8 clinical cases.
Miguel N, Costa E, Santalha M Jr, Lima R, Vizcaino JR, Pereira F, Barbot J.
J Pediatr Hematol Oncol. 2014 Mar;36(2):134-9.
[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

Nutrients. 2014 Nov 14;6(11):5117-5141.
Increasing Iron and Zinc in Pre-Menopausal Women and Its Effects on Mood and Cognition: A Systematic Review.
Lomagno KA и соавт.

Iron and zinc are essential minerals often present in similar food sources. In addition to the adverse effects of frank iron and zinc-deficient states, iron insufficiency has been associated with impairments in mood and cognition. This paper reviews current literature on iron or zinc supplementation and its impact on mood or cognition in pre-menopausal women. Searches included MEDLINE complete, Excerpta Medica Database (EMBASE), psychINFO, psychARTICLES, pubMED, ProQuest Health and Medical Complete Academic Search complete, Scopus and ScienceDirect. Ten randomized controlled trials and one non-randomized controlled trial were found to meet the inclusion criteria. Seven studies found improvements in aspects of mood and cognition after iron supplementation. Iron supplementation appeared to improve memory and intellectual ability in participants aged between 12 and 55 years in seven studies, regardless of whether the participant was initially iron insufficient or iron-deficient with anaemia. The review also found three controlled studies providing evidence to suggest a role for zinc supplementation as a treatment for depressive symptoms, as both an adjunct to traditional antidepressant therapy for individuals with a diagnosis of major depressive disorder and as a therapy in its own right in pre-menopausal women with zinc deficiency. Overall, the current literature indicates a positive effect of improving zinc status on enhanced cognitive and emotional functioning. However, further study involving well-designed randomized controlled trials is needed to identify the impact of improving iron and zinc status on mood and cognition.

[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

Назначение празолов у пациентов с ССЗ повышает риск развития анемии:

Use of Proton Pump Inhibitors Is Associated With Anemia in Cardiovascular Outpatients
[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

Повышенный уровень С-реактивного белка у пациентов с воспалительным заболеванием кишечника и ЖДА может быть индикатором плохого/замедленного ответа на лечение пероральными препаратами железа, тогда как ответ на в/в введение железа не зависел от уровня С-реактивного белка:

Dig Dis Sci. 2014 Dec 12.
Clinical Significance of C-Reactive Protein Levels in Predicting Responsiveness to Iron Therapy in Patients with Inflammatory Bowel Disease and Iron Deficiency Anemia.
Iqbal T1, и соавт.
BACKGROUND: Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD). In clinical practice, many patients receive initial treatment with iron tablets although intravenous (i.v.) iron supplementation is often preferable.
AIM: This study investigated whether systemic inflammation at initiation of treatment (assessed by C-reactive protein [CRP] and interleukin-6 [IL-6] measurements) predicts response to iron therapy.
METHODS: Data from a previously published phase III trial were retrospectively analyzed after stratification of patients according to baseline CRP (>4 vs. ≤4 mg/L) and IL-6 (>6 vs. ≤6 pg/mL) levels. The study population consisted of patients with Crohn's disease or ulcerative colitis and IDA (Hb ≤ 110 g/L and TSAT < 20 % or serum ferritin < 100 ng/mL), randomized to either oral (ferrous sulfate) or i.v. iron (ferric carboxymaltose).
RESULTS: A total of 196 patients were evaluated (oral iron: n = 60; i.v. iron: n = 136). Baseline CRP and IL-6 levels were independent of patients' initial Hb levels and iron status (serum ferritin and TSAT; all p > 0.05). Among iron tablet-treated patients, Hb increase was significantly smaller in the high- versus low-CRP subgroup (1.1 vs. 2.0, 2.3 vs. 3.1, and 3.0 vs. 4.0 g/dL at weeks 2, 4, and 8, respectively; all p < 0.05). Differences were less pronounced with stratification according to baseline IL-6. Response to i.v. iron was mainly independent of inflammation.
CONCLUSIONS: Patients with high baseline CRP achieved a lower Hb response with oral iron therapy. Our results suggest that CRP may be useful to identify IBD patients who can benefit from first-line treatment with i.v. iron to improve their IDA.

[Dr.Vad]

В полной версии результаты исследования нагрузочного теста 200 мг железа фумаратом у мужчин и женщин - при норм. усвоении через 4 ч пик концентрации железа увеличивается примерно вдвое, интересно, что после приема 3-валентного железа такого повышения не отнечалось (железо-3 не следует применять для нагруз. теста):

Swiss Med Wkly. 2015 Jan 22;145:w14063.
Reference values for oral iron absorption of bivalent iron in healthy volunteers
[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

Популяционное исследование показало, что предшествующая ЖДА умеренно повышает риск развития венозного тромбоза:

Blood Coagul Fibrinolysis. 2015 Feb 13.
Association between venous thromboembolism and iron-deficiency anemia: a population-based study.
Hung SH, Lin HC, Chung SD.
Although iron-deficiency anemia (IDA) as a rare cause of cerebral sinus thrombosis was supported by several studies, the relationship between IDA and venous thromboembolisms (VTEs) remains unclear. In this study, we evaluated the association between IDA and subsequent VTEs based on a population-based coverage database. We retrieved data for this case-control study from the Taiwan Longitudinal Health Insurance Database 2000. In total, 2522 cases with VTE and 12 610 randomly selected controls were included. A conditional logistic regression was used to examine the association of VTEs with previously diagnosed IDA. The χ test indicated that there was a significant difference in the prevalence of prior IDA between subjects with a VTE and the controls (3.41 vs. 2.06%, respectively, P < 0.001). The conditional logistic regression analysis showed that the odds ratio (OR) of previous IDA for subjects with a VTE was 1.43 [95% confidence interval (CI): 1.10-1.87] compared with the controls after adjusting for monthly income, geographic region, urbanization level, cancer, inflammatory bowel disease, heart failure, hypertension, diabetes, coronary heart disease, hyperlipidemia, renal disease, obesity, and whether or not a subject was hospitalized and whether or not a subject had suffered from a fracture within 1 year prior to the index date. The adjusted OR for prior IDA in subjects with deep-vein thrombosis was 1.43 (95% CI: 1.08-1.90) compared with the controls. However, there was no significant difference in the adjusted OR of prior IDA between subjects with a pulmonary embolism and the controls (OR: 1.10; 95% CI: 0.63-1.92). We concluded that there was an association between IDA and VTEs.

[Dr.Vad]

Интересные результаты работы применения больших доз железа (180-200 мг/сут) для лечения ЖДА были представлены на последней АSH-2014: прирост гемоглобина на >10 г/л за две недели говорил о хорошем терапевтическом ответе и, то что препараты железа следует принимать и далее, тогда как ответ в виде прироста менее 10 г/л - о плохом/недостаточном усвоении железа и желательности перехода на в/в введение:

Introduction: Oral iron supplementation is an effective means of iron replacement. Nevertheless, there is a frequent need to transition patients with iron deficiency anemia (IDA) from oral to intravenous (IV) iron therapy for inadequate response. No definitive guidance on the optimal timing for this change in therapy exists. Serum hepcidin may be a marker in predicting response to oral iron therapy, but currently, hepcidin assays are not commercially available. We evaluated the ability of various early response characteristics to accurately predict for an overall hemoglobin (Hb) response to oral iron. Our objective was to identify an early predictor of overall Hb response in patients on oral iron treatment as a guide to the decision to switch from oral to IV iron in patients unlikely to benefit from continued oral iron.

Methods: Proprietary datasets from 6 published randomized studies in which oral iron (325 mg of ferrous sulfate containing 65 mg of elemental iron, t.i.d.[4 studies], 304.3 mg capsules containing 100 mg bivalent iron b.i.d [1 study] and as prescribed by the investigator [1 study]) was used as a comparator to ferric carboxymaltose were analyzed. Five studies were pooled into one primary analysis dataset and one study was analyzed separately due to differences in study design that precluded pooling. Patients were grouped by the underlying etiology of their IDA (postpartum, heavy uterine bleeding, gastrointestinal, and others) and stratified by those who had ≥ 1 g/dL Hb change after 14 days of oral iron therapy (responders) and those who did not (non-responders). Further analyses evaluated Hb response at various time points based on initial 14 day Hb response (≥ 1 g/dL change vs < 1 g/dL). We systemically evaluated changes in hemoglobin, absolute reticulocyte count, % reticulocyte count, ferritin, and transferrin saturation at specific time points to determine their ability to predict overall Hb response.

Results: A total of 738 patients who were randomized to oral iron were included in the pooled study analysis. In the separate study, a total of 253 patients, all non-responders, were included. The mean baseline values for the 6 studies were Hb 9.9 g/dL, ferritin 19.9 ng/mL, and TSAT 16.9%. The vast majority of patients (96%) were females with a mean age of 36 years. In the pooled analysis, by day 14 of oral iron treatment, 27.2% (201/738) of patients had a Hb increase of < 1 g/dL (non-responders). Of these 201 patients, less than half (46.8%, 94/201) achieved an increase in Hb ≥ 1 g/dL from baseline after 2 additional weeks of oral iron (by day 28) and only 63.2% (127/201) had an increase in Hb ≥ 1g/dL from baseline after 6 to 8 weeks of oral iron (42 to 56 days). Furthermore, only 27.4% (55/201) and 5.5% (11/201) had an increase in Hb of 2 or 3 g/dL respectively at the Day 42 or 56 measurement. In comparison, responders (those who had a Hb increase ≥ 1 g/dL by 14 days of treatment) sustained a robust Hb response with continued dosing of oral iron. After 4 weeks of oral iron (28 days), 84.9% of the responders had a ≥ 2 g/dL increase in Hb from baseline. After 6 to 8 weeks of oral iron (42 or 56 days), 92.9% of the patients had ≥ 2 g/dL Hb increase from baseline, significantly different from non-responders (p < 0.0001). Patients with etiology of postpartum anemia had the most robust Hb response to oral iron. Results observed in the sixth study were similar to the pooled analysis. Only 10.2% (17/167) of non-responders who continued oral iron after day 14 achieved a Hb ≥ 2g/dL by Day 35, whereas 38.8% (57/147) who were switched to IV ferric carboxymaltose achieved a Hb > 2/dL by Day 35 (p =0.0001). Hb response after 14 days of oral iron was a strong predictor of overall response (sensitivity = 90.1%, specificity = 79.3%, positive predictive value = 92.9%, negative predictive value= 72.7%), surpassing other parameters evaluated in this study.

Conclusion: In the absence of significant continuous blood loss, Hb measurements taken 14 days after initiation of oral iron therapy can reliably predict overall response in Hb to oral iron therapy. Accordingly, day 14 Hb may be a useful tool for clinicians in determining when to switch patients from oral to IV iron.

Abstract 211
Clinical Criteria for Transitioning from Oral to IV Iron Replacement Therapy in Patients with Iron Deficiency Anemia

[Dr.Vad]

Нормоцитарная анемия (при подтверждении отсутствия сочетания микро/макроцитоза, увеличения ретикулоцитов или низкого эритропоэтина) в разных клинических ситуациях в 80-90% отвечала ВОЗ-критерию железодефицитной (прирост гемоглобина на >5 г/л на фоне приема железа внутрь или в/в) несмотря на нормальный уровень ферритина (в среднем 127 мкг/л ; медиана: 85 - от 3 до 581 мкг/л); коррекция анемии зависела от исходного уровня гемоглобина: ~80% если он был снижен на <10 г/л и 25-40% если снижение было более выраженным:

Introduction
Normocytic anemia is a common type of anemia, with increasing prevalence in old age. However, diagnosing the etiology of normocytic anemia can be a challenge, as it is a clinical presentation for a vast variety of diseases. Physicians often commence extensive laboratory testing to exclude other differential diagnosis. Although nutritional (iron or vitamin B12/folate) deficiencies are typically associated with microcytic or macrocytic anemia, these deficiencies are readily treatable and iron deficiency is the most common form of anemia worldwide. Therefore, we would like to evaluate the prevalence of iron deficiency in patients initially presented with normocytic anemia.

Methods

This study is a retrospective chart review of patients being referred to an academic hematology clinic from 2003 to 2014 for further evaluation of chronic normocytic anemia without abnormalities in other cell lines. Following initial workup to ensure the absence of 1) mixed microcytic-macrocytic anemia, 2) reticulocytosis, and 3) low erythropoietin level, all patients received a therapeutic trial of iron orally or intravenously. A total of 125 patients (median age: 71 years, range: 24 – 97) had complete records before and after iron therapy for further analysis to determine the changes in hematological parameters and iron indexes.

The patients were categorized by the severity of their anemia, as defined by pretreatment hemoglobin levels below a given age and gender-specific normal range: (1) Hb ≤ 10.0 g/L below normal (n = 54), (2) Hb 10.1 – 20.0 g/L below normal (n = 37), Hb 20.1 – 30.0 g/L below normal (n = 21) and Hb > 30.1 g/L below normal (n = 14). Furthermore, the WHO definition of an increase of Hb ≥ 5.0 g/L was used to signify a response to iron replacement, which might be associated with a subjective improvement in general well-beings.

Results

The overall response rate to iron replacement therapy was 85.6%, and the anemia was fully corrected in 54.4% of the patients. The average pretreatment ferritin level for these patients was 127 μg/L (median: 85 μg/L, range 3 – 581 μg/L), which would generally not be considered indicative of iron deficiency. Additionally, the response rates among different subgroups were from 83% to 93%, where the percentage of responders was similar when comparing the mild anemic group (Hb ≤ 10.0 g/L below normal) and the more severe anemic groups. In contrast, although more than 80% of patients with mild normocytic anemia achieved a normal Hb after iron replacement, only 30-40% of patients with moderate to severe anemia (> 10 g/L below normal) experienced a normalization of Hb after iron therapy.

Conclusion

This retrospective case series illustrates that iron deficiency is a common and treatable cause in patients with chronic normocytic anemia. Despite the dogma that patients are unlikely to be iron deficient with a ferritin level ≥ 100 ug/L, more than 80% of patients in this study had an increase in Hb ≥ 5 g/L when iron stores were replenished. The data also suggests that a therapeutic trial of iron replacement should be considered in patients with mild normocytic anemia before extensive workup. However, as the anemia was likely multifactorial in patients with more severe normocytic anemia (with Hb > 10 g/L below the normal range) the benefits of an iron replacement trial should be balanced against the risks of iron overload if patients ultimately require regular blood transfusion for other concomitant hematological disorders.

Abstract 4032
Iron Deficiency As a Common Treatable Cause of Chronic Normocytic Anemia

[Dr.Vad]

Железа сульфат, принимаемый внутрь для лечения ЖДА, повышает риск побочных эффектов со стороны ЖКТ в 2.5-3 раза по сравнению с плацебо или в/в введением препарата железа, и риск этих поб. явлений не зависит от дозы; подробнее

Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

диагноз ЖДА и выявление злокачественных опухолей через 5 лет или позже: повышен в 1.5-2 раза риск развития рака поджелудочной, печени, почек, мочевого пузыря - результаты популяционного исследования из Тайваня:

PLoS One. 2015 Mar 17;10(3):e0119647.
Risk of Cancer in Patients with Iron Deficiency Anemia: A Nationwide Population-Based Study.
Hung N и соавт.
OBJECTIVE: This study evaluated the risk of cancer among patients with iron deficiency anemia (IDA) by using a nationwide population-based data set.
METHOD: Patients newly diagnosed with IDA and without antecedent cancer between 2000 and 2010 were recruited from the Taiwan National Health Insurance Research Database. The standardized incidence ratios (SIRs) of cancer types among patients with IDA were calculated.
RESULTS: Patients with IDA exhibited an increased overall cancer risk (SIR: 2.15). Subgroup analysis showed that patients of both sexes and in all age groups had an increased SIR. After we excluded patients diagnosed with cancer within the first and first 5 years of IDA diagnosis, the SIRs remained significantly elevated at 1.43 and 1.30, respectively. In addition, the risks of pancreatic (SIR: 2.31), kidney (SIR: 2.23), liver (SIR: 1.94), and bladder cancers (SIR: 1.74) remained significantly increased after exclusion of patients diagnosed with cancer within 5 years after IDA diagnosis.
CONCLUSION: The overall cancer risk was significantly elevated among patients with IDA. After we excluded patients diagnosed with IDA and cancer within 1 and 5 years, the SIRs remained significantly elevated compared with those of the general population. The increased risk of cancer was not confined to gastrointestinal cancer when the SIRs of pancreatic, kidney, liver, and bladder cancers significantly increased after exclusion of patients diagnosed with IDA and cancer within the first 5 years. This finding may be caused by immune activities altered by IDA. Further study is necessary to determine the association between IDA and cancer risk.

[Dr.Vad]

Клинический опыт врачей из Турции показывает, что у людей с дефицитом кобаламина нередко имеется и замаскированный дефицит железа, который демаскируется после успешного лечения В12 дефицита:

75 patients who were diagnosed with cobalamin deficiency were enrolled in this study. Complete blood counts and serum levels of iron, unsaturated iron binding capacity (UIBC), ferritin, vitamin B12, and thyroid stimulant hormone were determined at diagnosis and after cobalamin therapy. Patients who had a combined deficiency at diagnosis and after cobalamin therapy were recorded. Before cobalamin therapy, we found increased serum iron levels (126.4 ± 63.4 µg/dL), decreased serum UIBC levels (143.7 ± 70.8 µg/dL), increased serum ferritin levels (192.5 ± 116.4 ng/mL), and increased transferrin saturation values (47.2 ± 23.5 %). After cobalamin therapy, serum iron levels (59.1 ± 30 µg/dL), serum ferritin levels (44.9 ± 38.9 ng/mL) and transferrin saturation values (17.5 ± 9.6 %) decreased, and serum UIBC levels (295.9 ± 80.6 µg/dL) increased. Significant differences were observed in all values (p < 0.0001). Seven patients (9.3 %) had iron deficiency before cobalamin therapy, 37 (49.3 %) had iron deficiency after cobalamin therapy, and a significant difference was detected between the proportions of patients who had iron deficiency (p < 0.0001).
---
Indian J Hematol Blood Transfus. 2015 Jun;31(2):255-8.
Cobalamin deficiency can mask depleted body iron reserves.
Solmaz S, et al.
[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

Назначение Венофера (200 мг через день ) беременным женщинам на сроке 32-35 недель и средне-тяжелой степенью ЖД анемизации (гемоглобин 70-90 г/л, ферритин менее 12) эффективно повышает гемоглобин уже через две недели (+5.6 г/л), к концу третьей и четвертой недели прирост гемоглобина 14.4 и 20 г/л соответственно, и ко времени родов он составляет в среднем 112.4 г/л:

Gupta A, и соавт.
Role of intravenous iron sucrose in correction of anemia in antenatal women with advanced pregnancy.
Indian J Hematol Blood Transfus. 2015 Jun;31(2):251-4.
[Ссылки доступны только зарегистрированным пользователям ]

[Dr.Vad]

У каждого 3-его пациента с ЖДА можно выявить мигрень, которая также похоже связана с наличием беспричинного беспокойства и депрессией:

Wien Klin Wochenschr. 2015 Apr 9.
Is iron-deficiency anemia associated with migraine? Is there a role for anxiety and depression?
Pamuk GE и соавт.
BACKGROUND: In this study, we determined the frequency of migraine headache in iron-deficiency anemia (IDA) patients and whether it was related to anxiety, depression, and somatization.
METHODS: We included 127 consecutive IDA patients into the study. All patients were asked validated questions about headache and migraine face-to-face. They were administered validated questionnaires for anxiety-depression The Hospital Anxiety and Depression Scale and somatization. The quality of life (QoL) disturbance associated with headache was marked on a 0-10 VAS.
RESULTS: Of all IDA patients, 79.5 % defined headache at any time of their life. In addition, 36.2 % of all IDA patients defined the criteria for migraine. IDA patients with migraine were more frequently smokers and had significantly lower hemoglobin and mean corpuscular volume values (p values < 0.05). The IDA group with migraine had significantly higher mean anxiety score (p = 0.046) and headache-related QoL disturbance score (p = 0.021) than the IDA group without migraine. Migraine patients with aura had lower hemoglobin values (p = 0.02), higher depression scores (p = 0.005), and higher migraine-related QoL disturbance scores than others.
CONCLUSIONS: IDA patients have a high frequency of migraine headache. The presence of anxiety and depression have great influence on the presence of migraine in IDA patients.

[Dr.Vad]

ЖДА у молодых спортсменов или др. людей, занимающимися изнурительными тренировками или тяжелой физической работой - интересно, что в основе анемии может лежать сочетание физ. гемолиза, микропотерь крови через почки или ЖКТ, острофазовое нарушение усвоения из ЖКТ
и секвестрации железа в макрофагах; тогда как избыточная железо-потеря с потоотделением больше не рассматривается, как причина (на примере историй болезней у 3 человек):

Exercise-induced anaemia: a forgotten cause of iron deficiency anaemia in young adults
[Ссылки доступны только зарегистрированным пользователям ]