How to treat inflammatory bowel disease with anemia?

*Only for medical professionals to read for reference.
In the previous article, we explained how to diagnose and treat inflammatory bowel disease with anemia? Today we will talk about how patients with inflammatory bowel disease and anemia should be treated with intravenous iron supplementation
.

Inflammatory bowel disease (IBD) patients often have anemia, the incidence is between 6.
2%-73.
7% [1], European research shows that 42% of IBD patients develop anemia within the first year of diagnosis [2] ; The overall prevalence of anemia in IBD patients is about 24% [3]
.

In other words, 24 out of every 100 people with IBD have anemia
.

The common types of IBD-related anemia are iron deficiency anemia (IDA), anemia of chronic disease (ACD) and mixed type
.

Once IBD patients are diagnosed with IDA, iron supplementation should be started as soon as possible
.

There are two main ways to supplement iron: oral and intravenous
.

Oral iron is effective for patients with IBD disease, and can be used for IBD patients with mild anemia, who are in the inactive phase and have no previous intolerance of oral iron
.

However, oral iron has certain disadvantages.
Studies on IBD animal models have shown that through oral iron supplementation, the development of oxidative stress, disease activity, intestinal inflammation and even colorectal cancer is increased [4]
.

Intravenous iron supplementation has obvious advantages over oral iron.
For example: 1.
It does not need to be absorbed through the intestine and will not increase the burden on the gastrointestinal tract; 2.
A large amount of iron can directly enter the blood circulation in a short time, and the concentration of hemoglobin (Hb) can be rapidly increased.
; 3.
Short treatment time, fewer adverse reactions, better patient compliance, and definite curative effect; 4.
Compared with oral iron, it can better retain the microbial diversity of the intestinal tract
.

Therefore, patients with IBD, especially those with high disease activity or more severe anemia, tend to use intravenous iron
.

How to supplement iron intravenously? In Europe, intravenous iron supplementation is the standard first-line treatment for IBD-related iron deficiency [5]
.

Absolute indications for intravenous iron supplementation include: severe anemia (hemoglobin <10 g/dL), intolerance or adverse reactions to oral iron, severe intestinal disease activity, concomitant treatment of erythropoiesis, or patient preference [6 ]
.

There are six main types of intravenous iron agents: iron sucrose, iron carboxymaltose, iron glucuronate, low-molecular-weight iron dextran (LMWID), nano-iron oxide and iron isomalt[7]
.

For the above 6 kinds of iron agents, they are equally effective in treating inflammatory bowel disease complicated with anemia
.

The main difference is that it is affected by the frequency of patient visits.
If dialysis and chemotherapy patients need frequent visits, iron sucrose can be infused multiple times in small amounts
.

On the contrary, patients who do not need frequent visits can choose to use only 1-2 iron infusions, such as iron isomalt or low-molecular-weight iron dextran
.

For the usage and dosage of intravenous iron, please refer to the following calculation method: iron-deficiency anemia iron supplement dosage calculation = weight (kg) × (required HGB-actual HGB) (g/L) × 0.
24 + body iron reserve ( mg)
.

Iron sucrose usually requires multiple infusions.
Depending on the hemoglobin level, it is administered 2-3 times a week, 5-10 mL each time (100-200 mg iron), and the frequency of administration should not exceed 3 times a week
.

For patients with a history of drug allergy, it is recommended to give the test dose [1.
25 mL (25 mg)], slowly intravenously; other patients do not need to give the test dose
.

LMWID can be given in multiple doses, 2 mL each time (equivalent to 100 mg of elemental iron), or as a single total dose infusion
.

LMWID is currently the only intravenous iron that can be infused in a single large dose, which can reduce the number of infusions in patients [8]
.

The method is mainly to add 1 000 mg LMWID to 500 mL of normal saline, and slowly enter it for 4 to 6 hours
.

A study [9] showed that compared with the longer infusion time of iron sucrose from 30 to 210 minutes, the median infusion time of carboxymaltose iron was 15 minutes, and the infusion time was shorter (average 22 minutes, longest 75 minutes).
min) is also superior
.

Because iron carboxymaltose has significant advantages of high dose, high infusion speed and reduction of the need for repeated infusions, it is more conducive to the daily routine treatment of patients with IBD anemia
.

What are the adverse reactions of intravenous iron supplementation? (1) Allergic/hypersensitivity reactions: including dyspnea, hypotension, itching, and infusion-related reactions
.

All intravenous iron preparations are known to cause severe allergic reactions and may be fatal.
Avoid intravenous iron in patients with known severe anaphylactic shock
.

Studies have shown that high molecular weight iron dextran has a much higher incidence of allergic reactions than low molecular weight iron dextran [10-11]
.

However, by reducing the infusion rate, temporary hypotension or local burning sensation can be easily controlled [12]
.

(2) Hypophosphatemia: Hypophosphatemia caused by intravenous iron injection leads to osteomalacia
.

The entire series of biochemical changes caused by intravenous iron can be summarized as "6H syndrome"
.

1.
High fibroblast growth factor 23 (FGF-23), 2.
Hyperphosphateuria, 3.
Hypophosphatemia, 4.
Vitamin D deficiency, 5.
Hypocalcemia, 6.
Secondary hyperthyroidism Hyperparathyroidism
.

According to reports, the clinical manifestations of 6H syndrome secondary to osteochondrosis include osteomalacia, fractures, muscle weakness, and respiratory failure [13]
.

What should I pay attention to when taking intravenous iron? Although the advantages of intravenous iron supplementation are obvious, the following points should be paid attention to in clinical use: 1.
When giving the initial dose of intravenous iron therapy, the patient should be monitored within 60 minutes of infusion, and it should be equipped with cardiopulmonary resuscitation equipment and drugs.
Professionally trained medical staff will evaluate its serious adverse reactions
.

2.
Iron sucrose: for intravenous administration only, it is best to use intravenous drip to reduce the risk of hypotension and drug leakage
.

It is advisable to use the test dose for the first administration.
If there is no adverse reaction after 15 minutes of administration, continue to use up the remaining dose
.

Iron sucrose should be used immediately after dilution (1 mL diluted in 20 mL of normal saline), and the drip rate should be strictly controlled.
Every 100 mg of iron should be at least 15 minutes, 200 mg of iron should be at least 30 minutes, and 300 mg of iron should be at least 1.
5 hours, 400 mg iron should be instilled for at least 2.
5 hours, and 500 mg iron should be instilled for at least 3.
5 hours
.

For direct slow intravenous injection, the speed is 1 mL of undiluted liquid per minute (5 mL per ampoule takes 5 minutes), and one injection should not exceed 10 mL
.

3.
Iron dextran: In order to avoid allergic reactions, it is recommended to give 25 mg (iron content) as the test dose before the first treatment, and monitor the patient for at least 1 h
.

It can be injected intramuscularly or intravenously (only those with apparent molecular weight <200KD)
.

Before intravenous administration, 100-200 mg iron dextran was diluted with 0.
9% sodium chloride solution or 5% glucose solution to 10-20 mL for slow injection, or diluted to 100 mL for 4-6 h intravenous infusion
.

The pharmacist concluded: IBD patients often have anemia, which seriously affects the quality of life of the patients and requires intervention and treatment as soon as possible
.

IBD-related anemia is more common in IDA, and iron supplementation is the main method to correct anemia
.

There is growing evidence that intravenous iron supplementation is better than oral iron supplementation
.

With the continuous development of new dosage forms and the continuous improvement of treatment options, intravenous iron supplementation may replace oral iron supplementation as a more effective and safe treatment approach
.

Studies have shown that iron may increase the risk of infection, and the use of iron in patients with active IBD may aggravate infection and intestinal inflammation
.

Therefore, when IBD is in the acute infection period, iron supplementation should still be cautious
.

For more exciting content of inflammatory bowel disease, please lock in the digestive liver disease channel of the medical community~ see you in the next issue! References: [1] Wilson A, Reyes E, Ofman J.
Prevalence and outcomes of anemia in inflammatory bowel disease: a systematic review of the literature[J].
Am J Med, 2004, 116, Suppl 7A: 44S-49S.
[2]Burisch J,Vegh Z,Katsanos KH,et al;EpiCom study group.
Occurrence of Anaemia in the First Year of Inflammatory Bowel Disease in a European Population-based Inception Cohort-An ECCO-EpiCom Study[J].
J Crohns Colitis,2017,11(10):1213-1222.
[3]Filmann N,Rey J,Schneeweiss S,et al.
Prevalence of anemia in inflammatory bowel diseases in European countries:a systematic review and individual patient data meta-analysis[ J].
Inflamm Bowel Dis,2014,20(5):936-945.
[4]Schreiber S,Howaldt S,Schnoor M,et al.
Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease.
N Engl［J］ Med.
1996;334:619-623.
[5].
Jimenez K,Gasche C,Auerbach M.
On both sides of the ocean［J］.
Blood Transfus,2016,14(2):197-198.
DOI:10.
2450/2016.
0304-15.
[6].
Christoph Gasche,Arnold Berstad,et al.
Guidelines on the Diagnosis and Management of IronDeficiency and Anemia in Inflammatory Bowel Diseases［J］.
Inflamm Bowel Dis,Volume 13,Number 12,December 2007.
[7]Red Blood Cell Diseases (Anemia) Group of Hematology Branch of Chinese Medical Association.
Iron Deficiency and Iron Deficiency Anemia diagnosis, treatment and prevention multidisciplinary expert consensus.
Chinese Medical Journal, July 24, 2018, Vol.
98, No.
28 Natl Med J China, July 24 2018, Vol.
98, No.
28.
[8] Diane K.
Wysowski,* Lynette Swartz, B.
, et a1.
Use of parenteral iron products and serious anaphylactic-type reactions［J］.
American Journal of Hematology，85:650–654,2010.
[9]Jürgen Stein,a,e Ayşegül Aksan,a,f Wolfgang Klemm,et a1.
Safety and Efficacy of Ferric Carboxymaltose in the T reatment of Iron Deficiency Anaemia in Patients with Inflammatory Bowel Disease,in Routine Daily Practice［J］.
Journal of Crohn's and Colitis,2018,1–9.
[10]Chertow GM, Mason PD,Vaage-Nilsen O,Ahlmen J.
On the relative safety of parenteral iron formulations.
Nephrol Dial T ransplant 2004;19:1571–1575.
[11]Chertow GM,Mason PD,Vaage-Nilsen O,Ahlmen J.
Update on adverse drug events associated with parenteral iron.
Nephrol Dial T ransplant 2006;21:378–382.
[12]Christoph Gasche,MD;Clemens Dejaco,MD, et al;Intravenous Iron and Erythropoietin for Anemia Associated with Crohn Disease[J] .
15 May 1997•Annals of Internal Medicine•Volume 126•Numb[13]Zoller,H.
,Schaefer,B.
,Glodny,B.
,2017.
Iron-induced hypophosphatemia:an emerging complication.
Curr.
Opin.
Nephrol.
Hypertens.
26(4), 266–275.
Expert profile Professor Xiaocang Cao, chief physician and professor of the Department of Gastroenterology, Tianjin Medical University General Hospital, master tutor of Tianjin Medical University, doctor of Peking Union Medical College·Tsinghua University School of Medicine, Texas State University of Medicine, USA Postdoctoral Fellow, Postdoctoral Visiting Scholar of the Faculty of Medicine of the University of Lille, France Ahlmen J.
Update on adverse drug events associated with parenteral iron.
Nephrol Dial T ransplant 2006;21:378–382.
[12]Christoph Gasche,MD;Clemens Dejaco,MD,et al;Intravenous Iron and Erythropoietin for Anemia Associated with Crohn Disease[J].
15 May 1997•Annals of Internal Medicine•Volume 126•Numb[13]Zoller,H.
,Schaefer,B.
,Glodny,B.
,2017.
Iron-induced hypophosphatemia:an emerging complication.
Curr.
Opin.
Nephrol.
Hypertens.
26(4), 266–275.
Expert profile Professor Xiaocang Cao, chief physician and professor of the Department of Gastroenterology, Tianjin Medical University General Hospital, master tutor of Tianjin Medical University, doctor of Peking Union Medical College·Tsinghua University School of Medicine, Texas State University of Medicine, USA Postdoctoral Fellow, Postdoctoral Visiting Scholar of the Faculty of Medicine of the University of Lille, France Ahlmen J.
Update on adverse drug events associated with parenteral iron.
Nephrol Dial T ransplant 2006;21:378–382.
[12]Christoph Gasche,MD;Clemens Dejaco,MD, et al;Intravenous Iron and Erythropoietin for Anemia Associated with Crohn Disease[J].
15 May 1997•Annals of Internal Medicine•Volume 126•Numb[13]Zoller,H.
,Schaefer,B.
,Glodny,B.
,2017.
Iron-induced hypophosphatemia:an emerging complication.
Curr.
Opin.
Nephrol.
Hypertens.
26(4), 266–275.
Expert profile Professor Xiaocang Cao, chief physician and professor of the Department of Gastroenterology, Tianjin Medical University General Hospital, master tutor of Tianjin Medical University, doctor of Peking Union Medical College·Tsinghua University School of Medicine, Texas State University of Medicine, USA Postdoctoral Fellow, Postdoctoral Visiting Scholar of the Faculty of Medicine of the University of Lille, France
.

Member of the Digestive Endoscopy Committee of the Inflammatory Bowel Disease Group of the Chinese Medical Association of Gastroenterology, Vice Chairman of the Youth Committee of the Chinese Medical Association of Behavioral Medicine, Member of the Clinical Epidemiology Collaboration Group of the Chinese Medical Association of Digestive Medicine, Digestive Diseases of the Chinese Medical Equipment Association Member of the Inflammatory Bowel Disease Group of the Academic Subcommittee, Member of the Inflammatory Bowel Disease Professional Committee of the Anorectal Doctors Branch of the Chinese Medical Doctor Association, Member of the Inflammatory Bowel Disease Expert Committee of the Digestive Endoscopy Professional Committee of the Chinese Integrative Medicine Association, Beijing Member of the Inflammatory Bowel Disease Expert Committee of the Medical Award Foundation, Member of the Intestinal Microecology Professional Committee of the Wu Jieping Medical Foundation Inflammatory Bowel Disease Alliance, Member of the Standing Committee of the Stem Cell Engineering Technology Branch of the Chinese Society of Biomedical Engineering, Tianjin Medical Association of Digestive Science Inflammation The research direction of the deputy director of the Gastroenterology Group: Inflammatory bowel disease and digestive tract immune disease, autoimmune disease biological therapy and cell therapy, especially dedicated to the clinical application of mesenchymal stem cell transplantation
.

The research results have won awards from international conferences such as the American Digestive Academy Annual Meeting and the European Union Digestive Academy Annual Meeting, and dozens of papers have been published in SCI journals and Chinese journals
.

Xie Dong is a clinical pharmacist in the General Hospital of Tianjin Medical University, a clinical pharmacist in the Department of Gastroenterology, a national clinical pharmacist training base, and an MTM pharmacist certified by the American Pharmacists Association (APhA)
.

Wang Ping, clinical pharmacist of Tianjin Beichen Hospital
.