Interaction between ferric carboxymaltose and denosumab causing severe hypocalcaemia and hypophosphataemia in a patient without chronic kidney disease

Coadministration of ferric carboxymaltose and denosumab may cause hypocalcaemia and hypophosphataemia; however, this interaction is not well-described in the literature and has typically been described in patients with chronic kidney disease (CKD). We present a case of this interaction in a patient without preexisting CKD. We suggest the use of alternative iron preparations and an interval of at least 4 weeks between administrations.     

Pediatric Crohn's disease,iron deficiency anemia and intravenous iron treatment: a follow-up study

Background and aims: Increasing evidence in adults demonstrates efficacy and safety of IV iron in inflammatory Bowel disease (IBD) associated iron deficiency anemia; however, evidence in pediatric patients is yet scarce and no previous study has included a long follow-up. This study aimed to evaluate safety and efficacy of IV iron (primary end point), and the need of re-treatment (secondary end point), in this setting.

Methods: Prospective recruitment (40 months); PCDAI determined before and after treatment; anemia defined according to WHO criteria; IV iron treatment included iron sucrose and ferric carboxymaltose. Primary and secondary endpoints included hemoglobin, serum ferritin, transferrin saturation at baseline and 4-6 weeks after treatment; and the need of re-treatment during the median follow-up period (18 months), respectively.

Results: Nineteen patients (median age: 15.5 years) with remissive/mild disease were included. At recruitment, the median hemoglobin was 10.5?g/dl, (median s-ferritin: 20.1 ug/l, median transferrin saturation; 6%) and 4-6 weeks after treatment was 12.7?g/dl. Median hemoglobin according to age groups before vs. after treatment:?<12 years:11 vs. 12.0?g/dl; females ≥12 years:9.9 vs. 12.6?g/dl; and males ≥12 years:11.1 vs. 13.3?g/dl. Patients with remissive vs. mild disease had median Hb of 10.5?g/dl vs. 10.6?g/dl, and median s-ferritin: 6.8 ug/dl vs. 43.3 ug/dl, respectively). Nine patients were treated with iron sucrose (median dose 672.6?mg/dl) and 10 patients with ferric carboxymaltose (median dose 811.5?mg/dl). No major adverse reactions occurred. Six patients needed re-treatment after a median 15.5 months period.

Conclusions: Our prospective study, concerning pediatric IBD anemia patients with remission/mild disease and a significant follow-up, emphasizes efficacy and safety of IV-iron and the importance of long-term follow-up of iron status.

Summary: In pediatric IBD iron anemia, the evidence supporting the efficacy and safety of IV-iron is scare. This prospective study aims to evaluate the safety and efficacy (short and long term) of IV-iron in these patients. Nineteen pediatric CD patients were evaluated before and after IV iron treatment (40-month period).The median Hb before and after IV iron was 10.5 and 12.7?g/dl, respectively. No major adverse reactions were documented. Six patients needed re-treatment (median period of 15.5 months). This study further demonstrates the efficacy and safety of IV iron. It reinforces the importance of long-term follow-up of the iron status in pediatric CD patients.     

Inflammatory bowel disease and anemia: intravenous iron treatment

Objectives: The main objective of our study was to determinate the effectiveness of intravenous iron treatment with ferric carboxymaltose in inflammatory bowel disease (IBD) patients. Our other objectives were to study parameters that would predict a good response to the treatment and to chart out possible side-effects of the treatment.

Materials and methods: In our retrospective chart review study we collected clinical data and laboratory results related to IBD from medical records of 87 IBD patients who were treated with ferric carboxymaltose in Helsinki University Hospital between 2014 and 2016.

Results: The mean increase in hemoglobin levels of the patients was 24.6?g/l (+?24%) after one month, 27.6?g/l (+?27%) after three months and 26.0?g/l (+?27%) after six months. Nine out of 87 treated patients (10.3%) reported side-effects during the iron infusion. A linear regression model assessing the change in hemoglobin levels after six months demonstrated close correlation with transferrin receptor count (p?=?.004) and ferritin (p?=?.016) with an adjusted R square of 0.463.

Conclusion: Ferric carboxymaltose was found to be an effective and well tolerated treatment for iron deficiency anemia in patients with IBD. The results of our study further strengthen the current knowledge of the effectiveness and safety of the treatment.     

Management of iron deficiency in patients admitted to hospital: time for a rethink of treatment principles

Background: Iron deficiency is very common in patients admitted to hospital. Its management is changing with new insights into iron absorption and therapeutic options. Aims: The aims of this study were to develop guidelines for the correction of iron deficiency in patients admitted to hospital and to compare these with current practice. Methods: Based on current published evidence, guidelines were developed. All patients in whom iron deficiency was detected during hospital admission over a 2.5 year period were retrospectively studied. Their management was compared with that of the guidelines developed. Results: Three clinical scenarios were identified—(A) urgent attention to haemoglobin required: blood transfusion followed by i.v. iron recommended, (B) Semiurgent iron repletion: i.v. iron recommended and (C) non‐urgent iron repletion: oral or i.v. repletion recommended. A total of 119 patients was identified, age 18–99 (median 77) years, 29% men, and haemoglobin 33–130 (87) g/L. Of 66 given blood transfusion, 17 had subsequent i.v. iron, 25 oral iron and 24 no other form of iron repletion. Of the other 53, nine had i.v. iron, 32 oral iron and 12 had no treatment. Fifty‐five per cent of patients were managed according to the proposed guidelines and this occurred less frequently (9%) in those presenting with cardiovascular problems than in those with anaemia, gastrointestinal bleeding or other medical problems (all >60%; P < 0.0001, Fisher's exact test). Conclusion: Current management is haphazard, with underutilization of i.v. iron and failure to initiate any regimen for iron repletion being common. It may be time for a change in approach to repletion of iron in ill patients.     

High incidence of iron depletion and restless leg syndrome (RLS) in regular blood donors: intravenous iron sucrose substitution more effective than oral iron

Background and objectives Iron depletion is common in regular blood donors. The objective of the study was to investigate the frequency and severity of iron depletion in regular blood donors and whether IV iron is more effective than oral to avoid iron depletion and symptoms thereof, especially restless legs syndrome (RLS). Method One hundred and twenty blood donors with at least five previous whole blood donations were randomized to receive either IV iron sucrose (Venofer^®, RenaPharma/Vifor, Uppsala, Sweden), 200 mg, or to 20 × 100 mg of oral iron sulphate (Duroferon^®, GlaxoSmithKline, Stockholm, Sweden), after each blood donation during 1 year. Iron status and RLS incidence and severity were investigated. Results Iron status was generally poor among regular blood donors, especially in women, with a high incidence of iron depletion (> 20%) and RLS (18%). The IV iron group increased storage iron to a greater extent than the oral iron group after 12 months (P = 0·0043). Female donors were more responsive to IV iron sucrose compared to oral iron sulphate, particularly female donors below 50 years of age. RLS severity scores were significantly lower in the IV iron group. The two treatments were safe. Conclusion Iron status is poor in regular blood donors, restless legs syndrome is common, and the routine iron supplementation is insufficient. IV iron sucrose substitutes iron loss in blood donors more efficiently compared with oral iron sulphate, especially in women. Iron substitution to blood donors should be individualized and based on P‐ferritin monitoring.     

Single-dose intravenous ferric carboxymaltose infusion versus multiple fractionated doses of intravenous iron sucrose in the treatment of post-operative anaemia in colorectal cancer patients: a randomised controlled trial

BackgroundRecent clinical guidelines suggest that treatment of postoperative anaemia in colorectal cancer surgery with intravenous iron reduces transfusion requirements and improves outcomes. The study aimed at comparing two intravenous iron regimens in anaemic patients after colorectal cancer surgery.Materials and methodsThis was a single-centre, open-label, randomised, controlled trial in patients undergoing elective colorectal cancer surgery. Patients with moderate to severe anaemia (haemoglobin [Hb] <11 g/dL) after surgery were randomly assigned 1:1 to receive ferric carboxymaltose (FC; 1,000 mg, single dose) or iron sucrose (IS; 200 mg every 48 hours until covering the total iron deficit or discharge). Randomisation was stratified by Hb level: <10 g/dL (Group A) or ≥10–10.9 (Group B). The primary endpoint was the change in Hb concentration at postoperative day 30. Secondary endpoints included iron status parameters, transfusion requirements, complications, and length of hospital stay.ResultsFrom September 2015 to May 2018, 104 patients were randomised (FC 50, IS 54). The median intravenous iron dose was 1,000 mg and 600 mg in the FC and IS groups, respectively. There were no between-group differences in mean change in Hb from postoperative day 1 to postoperative day 30 (FC: 2.5 g/dL, 95% CI: 2.1–2.9; IS: 2.4 g/dL, 95% CI: 2.0–2.8; p=0.52), in transfusion requirements or length of stay. The infection rate was lower in the FC group compared with the IS group (9.8% vs 37.2%, respectively).DiscussionThe administration of approximately 500 mg of IS resulted in an increase in Hb at postoperative day 30 similar to that of 1,000 mg of FC, but it was associated with a higher infection rate. Future research will be needed to confirm the results, and to choose the best regime in terms of effectiveness and side effects to treat postoperative anaemia in colorectal cancer patients.     

Prevalence of iron deficiency anemia and iron deficiency in a pediatric population with inflammatory bowel disease

Objectives: Iron deficiency is the most common cause of anemia in children with inflammatory bowel disease, although the real prevalence is unknown. Intravenous iron is suggested as the first line treatment. This study aims to determine the prevalence of iron deficiency anemia in children with inflammatory bowel disease followed in a Pediatric Gastroenterology Unit of a tertiary center and to evaluate this unit's experience with intravenous iron.

Materials and methods: A retrospective cohort study was designed involving children with inflammatory bowel disease followed in that unit between January 2001 and April 2016. Laboratory results were collected at the moment of diagnosis, after one-year follow-up and prior each IV iron administration performed during the study period. Anemia was defined according to World Health Organization criteria and the iron deficiency was defined using recent guidelines.

Results: Were studied 69 patients 71% had CD and 29% UC. 50.7% were female. Mean patient age at diagnosis was 13.3 years (range 1--17 years). Prevalence of ID and IDA at diagnosis was 76.8% and 43.5%, respectively. After one year follow-up, those values decreased to 68.1% (p?=?.182) and 21.7% (p?=?.002), respectively. Hemoglobin significantly increased (p?<?.001). Intravenous iron was administered to 92.8% of patients. No adverse reactions were reported.

Conclusions: Intravenous iron is the first line in the treatment of Iron deficiency anemia in Inflammatory Bowel disease and it is safe and effective. Persistent anemia and iron deficiency are common.     

Effect of intraoperative intravenous ferric derisomaltose supplementation on reduction of postoperative anemia and transfusion in chronic kidney disease patients after total knee replacement

Total knee replacement (TKR) is associated with a large amount of bleeding; therefore, the prevalence of postoperative anemia is high. In particular, patients with chronic kidney disease (CKD) are more vulnerable to postoperative anemia than are healthy individuals. Accordingly, the effect of intraoperative intravenous ferric derisomaltose (FDI) supplementation on postoperative anemia and blood transfusion volume reduction in patients with CKD was studied. Patients who underwent unilateral TKR between January 2019 and December 2020 were retrospectively reviewed. In analyzing the data, the patients fell into the CKD group (n = 85) and the non-CKD group (n = 106). Each group was divided into a group using FDI and a non-FDI group, and classified into 4 groups. The postoperative hemoglobin level for each postoperative day (POD) was determined as the primary outcome. In addition, the patient transfusion rate, volume of transfusion, and length of hospital stay were set as secondary study outcomes during the period from surgery to discharge. There was no statistically significant difference in hemoglobin levels on PODs 0, 1, 2, 7, and 14 in the CKD group. In the CKD group, the transfusion volume of the FDI group was 0.58 ± 0.91 units per person, which was statistically significantly lower than 1.28 ± 1.28 units of the non-FDI group (P = .01). In the CKD group, the transfusion rate of the FDI group was 30.2%, which was statistically significantly lower than that of the non-FDI group, which was 56.3% (P = .02). This study showed that intravenous FDI supplementation after TKR in CKD patients did not reduce postoperative anemia but was an effective and safe treatment to reduce transfusion volume and transfusion rate. There was no statistically significant difference in hemoglobin levels on POD 0, 1, 2, 7, and 14 in the non-CKD group. In the non-CKD group, the transfusion volume of the FDI group was 0.46 ± 0.88 units per person, which was lower than the 0.56 ± 0.91 units of the non-FDI group, but it was not statistically significant (P = .59). In the non-CKD group, the transfusion rate of the FDI group was 23.0%, which was lower than that of the non-FDI group, which was 31.3%, but it was not statistically significant (P = .37).     

Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion

Anaemia is a common condition among patients admitted to hospital medicosurgical departments, as well as in critically ill patients. Anaemia is more frequently due to absolute iron deficiency (e.g. chronic blood loss) or functional iron deficiency (e.g. chronic inflammatory states), with other causes being less frequent. In addition, preoperative anaemia is one of the major predictive factors for perioperative blood transfusion. In surgical patients, postoperative anaemia is mainly caused by perioperative blood loss, and it might be aggravated by inflammation-induced inhibition of erythropoietin and functional iron deficiency (a condition that cannot be corrected by the administration of oral iron). All these mechanisms may be involved in the anaemia of the critically ill. Intravenous iron administration seems to be safe, as very few severe side-effects were observed, and may result in hastened recovery from anaemia and lower transfusion requirements. However, it is noteworthy that many of the recommendations given for intravenous iron treatment are not supported by a high level of evidence and this must be borne in mind when making decisions regarding its application to a particular patient. Nonetheless, this also indicates the need for further large, randomized controlled trials on the safety and efficacy of intravenous iron for the treatment of anaemia in different clinical settings.     

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

Background

Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED.

Materials and methods

From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes.

Results

Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed.

Discussion

Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.     

Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective,matched cohort study

Background

Requirements for allogeneic red cell transfusion after total lower limb arthroplasty are still high (20–50%), and post-operative intravenous iron has been shown to reduce transfusion requirements for this surgery. We performed a cost analysis to ascertain whether this alternative is also likely to be cost-effective.

Materials and methods

Data from 182 matched-pairs of total lower limb arthroplasty patients, managed with a restrictive transfusion protocol and without (control group) or with post-operative intravenous iron (iron group), were retrospectively reviewed. Acquisition and administration costs of iron (iron sucrose or ferric carboxymaltose) and allogeneic red cell concentrates, haemoglobin measurements, and prolonged stay in hospital were used for blood management cost analysis.

Results

Patients in the iron group received 600 mg intravenous iron, without clinically relevant incidents, and had a lower allogeneic transfusion rate (11.5% vs 26.4% for the iron and control groups, respectively; p=0.001). The reduction in transfusion rate was more pronounced in anaemic patients (17% vs 40%; p=0.015) than in non-anaemic ones (9.6% vs 21.2%; p=0.011). There were no differences with respect to post-operative infection rate. Patients receiving allogeneic transfusion stayed in hospital longer (+1.9 days [95% CI: 1.2–2.6]). As intravenous iron reduces the allogeneic transfusion rate, both iron formulations were cost-neutral in the different cost scenarios (−25.5 to 62.1 €/patient for iron sucrose, and −51.1 to 64.4 €/patient for ferric carboxymaltose).

Discussion

In patients presenting with or without pre-operative anaemia, post-operative intravenous iron after total lower limb arthroplasty seems to be safe and is associated with reduced transfusion rates, without incremental costs. For anaemic patients, its efficacy could be increased by associating some other blood-saving method.