Diagnosis and treatment of iron-deficiency anemia in gastrointestinal bleeding: A systematic review

Table 1 Characteristics of included original articles and meta-analyses

Ref.	Year	Study type	No of patients	GI etiology	No of males/females	Age	Study period
Bager et al[5]	2013	Retrospective	169	Nonvariceal AUGIB	86/83	70 (22-95)1	2009
Bager et al[44]	2014	Double-blind, randomized, placebo-control	97	Nonvariceal AUGIB	51/46	70 (23-95)2	2010-2013
Bager et al[50]	2014	Double-blind, randomized, placebo-control	97	Nonvariceal AUGIB	51/46	70 (67.4-73.1)3	-
Ballester et al[45]	2019	Retrospective, single-center	84	Acute GIB	58/26	68.0 (16.9)2	2012-2015
Bosch et al[51]	2017	Prospective cohort	2818	GI diseases known to cause GIB	1398/1420	63.4 (15.7)2	2015-2016
Bosch et al[29]	2017	Prospective cohort	4552	Occult bleeding	2266/2286	63.7 (17.6)2	2005-2015
Brooklyn et al[6]	2003	N/A	153	Occult bleeding	51/102	66 (45-96)2	2000
Cheng et al[52]	2010	Prospective	390	Ulcers	263/127	63 (16)2	-
El-Halabi et al[7]	2016	Retrospective, chart review, single-center	307	Any GIB	130/177	66.2 (18.6)2	2011-2012
Geisser et al[46]	2010	Phase I/II, multicenter, open-label, multiple-dose	46	Bleeding due to GI disorder	10/36	42.9 (11.0)2	2003-2004
Jairath et al[35]	2010	Meta-analysis	-	AUGIB	2731/1710	Early RBC 67.9 (16.51)2; no early RBC 63.4 (19.19)2	2007
Jairath et al[36]	2015	Pragmatic, multicentric, open-label, randomized feasibility trial	936	AUGIB	566/370	Liberal 60.4 (20.0)2; restrictive 58.0 (20.3)2	2012-2013
Restellini et al[31]	2013	Observational, registry-based	1677	Nonvariceal AUGIB	1035/642	66.2 (16.8)2	1999-2002
Rockey et al[32]	2017	Prospective cohort	1460	Acute or chronic GIB	899/561	53 (14)2	2006-2011
Salvadori et al[47]	2016	Retrospective	38	GI chronic blood loss	22/16	78 (54-94)4	2014-2015
Schröder et al[48]	2004	N/A	31	GI blood loss	12/19	43.8 (18.0)2	-
Subramaniam et al[30]	2016	Retrospective cohort	2360	Nonvariceal AUGIB	1505/852	70 (56-81)4	2008-2010
Villanueva et al[37]	2013	RCT	889	Severe AUGIB	-	-	2003-2009

¹The median (range).

²The mean (range) or mean (standard deviation).

³Mean (95% confidence interval).

⁴The median (Interquartile range). AUGIB: Acute upper gastrointestinal bleeding; GI: Gastrointestinal; GIB: Gastrointestinal bleeding; RBC: Red blood cell; RCT: Randomized controlled trial.

Table 2 Characteristics of the included guidelines

Guideline organization/society/authors	Year	GI etiology	Origin	Level of development
Iron-Deficiency Anemia Working Group Consensus Report[34]	2017	IBD and GIB	Turkey	Scientific committee/expert group
The International Consensus Upper Gastrointestinal Bleeding Conference Group[38]	2010	Nonvariceal UGIB	International	Scientific committee/expert group
Dahlerup et al[17] Guideline approved by the Danish Society of Gastroenterology and Hepatology	2014	GIB, various etiologies	Denmark	Independent authors and approved by a professional organization/society
Baveno IV Consensus Workshop[43]	2015	Variceal bleeding	International	Scientific committee/expert group
European Crohn's and Colitis Organization[10]	2015	IBD	Europe	Professional organization/society
Gasche et al[11]	2007	IBD	Europe	Scientific committee/expert group
British Society of Gastroenterology[12]	2011	-	United Kingdom	Professional organization/society
Hong Kong Society of Gastroenterology, the Hong Kong IBD Society, the Hong Kong Society of Digestive Endoscopy, and the Hong Kong Red Cross Blood Transfusion Service[13]	2018	Acute and chronic GIB	Hong Kong	Professional organization
The 2018 Patient Blood Management International Consensus Conference[39]	2019	Acute GIB	Germany	Scientific committee/expert group
British Society of Gastroenterology[40]	2019	ALGIB	United Kingdom	Professional organization
National Institute for Health and Care Excellence[41]	2015	-	United Kingdom	Professional organization
Strate et al[42]	2016	ALGIB	United States and Israel	Independent authors
World Health Organization[33]	2001	-	International	Professional organization

ALGIB: Acute lower gastrointestinal bleeding; GIB: Gastrointestinal bleeding; IBD: Inflammatory bowel disease; UGIB: Upper gastrointestinal bleeding.

Table 3 Erythrocyte transfusion: Guidelines for hemoglobin thresholds and targets

Professional association	GI etiology	Threshold Hb, g/dL	Threshold Hb cardiovascular disease, g/dL	Target Hb, g/dL	Target Hb cardiovascular disease, g/dL
The International Consensus Upper Gastrointestinal Bleeding Conference Group[38]	Nonvariceal UGIB	< 7	-	-	-
Baveno IV Consensus Workshop[43]	Variceal bleeding	7-8	-	-	-
European Crohn's and Colitis Organization[10]	IDA in IBD	< 7	-	-	-
Hong Kong Society of Gastroenterology, the Hong Kong IBD Society, the Hong Kong Society of Digestive Endoscopy, and the Hong Kong Red Cross Blood Transfusion Service[13]	Acute UGIB	7-8	9-10	-	-
The 2018 Patient Blood Management International Consensus Conference[39]	Acute GIB	7-8	-	-	-
British Society of Gastroenterology[40]	Acute LGIB	< 7	8	7-9	10
National Institute for Health and Care Excellence[41]	N/A	< 7	8	7-9	8-10
Strate et al[42]	Acute LGIB	-	9	> 7	> 9

GIB: Gastrointestinal bleeding; Hb: Hemoglobin; IBD: Intestinal bowel disease; IDA: Iron-deficiency anemia; LGIB: Lower gastrointestinal bleeding; UGIB: Upper gastrointestinal bleeding.

Table 4 Pharmacological characteristics, advantages and disadvantages of worldwide available oral and intravenous iron preparations

Type of preparation	Advantages	Disadvantages
Oral	Safe; readily available (does not require a prescription); administered at home; inexpensive; effective when intestinal absorption is not impaired; no need for venous access and infusion monitoring; eliminates the risk of infusion reactions	Slower repletion of iron stores; Intestinal absorption is relatively low, and may be impaired by concomitant food and medications; gastrointestinal adverse events, including constipation, dyspepsia, bloating, nausea, diarrhoea, heartburn, reducing tolerance and adherence to treatment; compliance difficulted by high pill burden (typically three tablets/day) and gastrointestinal intolerance; diminished efficacy when the uptake is impaired (e.g., in celiac disease, autoimmune gastritis, anemia of chronic disease, or post–gastric or duodenal resection)
Ferric hydroxide polymaltose complex
Sodium ferric gluconate
Ferrous gluconate
Ferrous sulfate
Ferrous fumarate
Intravenous	Fast repletion of iron stores; safe when avoiding preparations with dextran; very effective; gastrointestinal adverse events less frequent; ferric carboxymaltose, iron isomaltoside 1000, and ferumoxytol are considered more stable	Administration by a health care professional, requiring clinic visits; increased costs per dose, but fewer doses required; risk of iron overload and transient increase in oxidative stress; risk of anaphylactic reactions with dextran-containing preparations; risk of hypersensitivity reactions
Ferric gluconate
Iron sucrose
Low molecular weight iron dextran
Ferric carboxymaltose
Iron isomaltoside 1000
Ferumoxytol

Adapted from Muñoz et al[25], Drozd et al[26], Jimenez et al[27], McDonagh et al[28].

Table 5 Calculation of iron requirement according to patient body weight and hemoglobin level

Hemoglobin (g/dL)	Hemoglobin (mmoL/L)	Patient body weight (below 35 kg)	Patient body weight (35 kg to 70 kg)	Patient body weight (70 kg and above)
< 10	< 6.2	500 mg	1500 mg	2000 mg
10 to 14	6.2 to 8.7	500 mg	1000 mg	1500 mg
≥ 14	≥ 8.7	500 mg	500 mg	500 mg

Adapted from Infarmed[49], 2015.