3rd Mediterranean Multidisciplinary Course on Iron Anemia

Figures & data

Figure 1. Causes of anemia in the cancer patient.

Figure 1. Physiopathology of anemia of chronic diseases.

Table 1. Comparative cost-efficacy of different iv. iron formulation for treating IBD-associated anemia.

IV iron formulation (Ref.)		IS-1 [10]	IS-2 [11]	FCM-1 [11]	FCM-2 [12]	MNF-I [13]	MNF-B [13]	LMWID [14]
Patients		45	235	240	136	108	111	33
Hb baseline (g/dl)		10.5	10.3	10.1	8.7	9.7	9.5	9.3
Hb 8 weeks(g/dl)		12.1	12.6	12.9	12.5	12.2	12.3	11.3
ΔHb (g/dl)		1.60	2.30	2.80	3.80	2.43	2.73	2.01
Dose IV iron/patient (mg)		960	1160	1377	1405	885	883	949
Dose IV iron/session (mg)		200	200	500-1000	200-1000	250-1000	250-500	20 mg/kg
Sessions/patient		4.8	5.8	2.1	1.7	1.2	2.0	1.0
Cost 100 mg IV iron (€)		8.5	8.5	20	20	20	20	10.3
Administration costs per session [15]	- Personnel - Materials - Others	22.5 7.0 17.5	22.5 7.0 17.5	13.5 7.0 14.5	13.5 7.0 14.5	13.5 7.0 14.5	10.5 3.0 3.5	34–88 19–37 156–228
Treatment cost per patient		307	371	349	338	218	194	148–240
Treatment cost Δg/dl Hb		192	161	125	89	90	71	74–120

FCM: Ferric carboxymaltose; IS: Iron sucrose; LMWID: Low-molecular-weight iron dextran; MNF: Iron isomaltoside-1000.

Table 1. Demographic characteristics.

Characteristic	Group A iv. iron	Group 8 Liposomal iron	Group C No iron
Male/female	9/11	12/8	2/2
Median age, years	73 (range 62--75)	65 (range 59--70)	71 (range 60--74)
Karyotype	Normal 10 Not evaluable 10	Normal 12 Not evaluable 8	Normal 3 Not evaluable 1
Comorbidities	NIDDM 14 COPD 10 CHF 1	NIDDM 10 COPD 4 CHF 2	NIDDM 3 COPD 1 CHF 0
Median Hb level	9.3 g/dl (R 8.6-11)	8.8 g/dl (R 8-11.5)	8.7 g/dl (R 8.5-9.5)
Basal epoetin level	Availability 6/20 (30%) Inappropriate 2/6 (33%)	Availability 9/20 (45%) Inappropriate 4/9 (44%)	Availability 1/4 (25%) Inappropriate 0/1 (0%)

COPD: Chronic obstructive pulmonary disease; CHF: Chronic heart failure; NIDDM: Non-insulin-dependent diabetes mellitus.

Table 2. Details of costs per patient.

CBC + Clinical chemistry tests + iron balance + B12 + folates + materials needed for sampling (sampling needle + gauze + test tube + disinfectant) + prescription: €70 Infusion tubing with drip adjuster: €0.43 Normal saline solution, 250 cc: €0.90 Gauze: €0.01 1 day of admission to day hospital (including nursing support and board): €200 Medical care for 1 day of day hospital: €140 1 lost working day: €584 Patient payment for clinic visit: €25 Cost per clinic room visit: €16/day Cost of 1 unit of concentrated red blood cells or platelets: around €200 Erythropoietin: approximately €500/ampoule Intravenous iron: approximately: €0.95 ampoule Liposomal iron, oral (Sideral RM): approximately € 1/ampoule

Table 3. Summary of main results.

Results	Group A iv. iron	Group B liposomal iron	Group C no iron
Median number of transfusions/month	1.5	1.5	2
Response to epoetin treatment	10 patients (50%)	9 patients (45%)	1 patient (25%)
Side effects	1 headache 3 hypotension 1 urticaria	2 G1-G2 diarrhoea	no
Patients transfused	12 (60%)	9 (45%)	3 (75%)
Median time for increase of 1 g/dl of Hb level after epo	4 weeks (range 4-9)	5 weeks (range 3–8)	6 weeks (range 3–9)
Time to reduction epo after achievement of 12 g/dl	12 weeks (range 4-18)	10.5 weeks (range 3–16)	I3 weeks (range 4–19)
Interval of maintenance dose	2 weeks (range 2-4)	3 weeks (range 2–5)	1.5 weeks (range 1–2)
Medían loss of days of work/month	7	0.08 (2 h/month)	10
Lack of Epo response	2 patients	3 patients	2 patients
Number of patients requiring iron retreatment	12 patients	9 patients	-

Table 4. Median monthly costs in Euros for each treatment group.

(n)	IV iron (20)	Liposomal iron (20)	No iron (4)
Blood tests	82	23	120
Iron therapy	6065	10	0
Infusion	47	0	0
Working days lost	390	28	650
Medical and nursing care in clinic or day hospital	93	6	87
Patient payment	2	7	7
Clinic	0	2	0
Transfusions	300	100	550
Erythropoietin	1800	1350	1800
Total monthly expenditure (€)	2720	1526	3214

Table 1. Preoperative correction of anemia of “Management of severe perioperative bleeding ESA Guidelines”.

We recommend that patients at risk of bleeding are assessed for anemia 4–8 weeks before surgery. 1C

If anemia is present, we recommend identifying the cause (iron deficiency, renal deficiency or inflammation). 1C

We recommend treating iron deficiency with iron supplementation (oral or intravenous). 1B

If iron deficiency has been ruled out, we suggest treating anaemic patients with erythropoietin-stimulating agents. 2A

If autologous blood donation is performed, we suggest treatment with erythropoietin-stimulating agents in order to avoid preoperative anemia and increased overall transfusion rates. 2B.

Table 2. Summary of recommendations related to anemia of the Spanish Update Consensus Document on alternatives to reduce allogeneic blood transfusion (in descending order of strength).

We recommend:

Grade 1A recommendations - The administration of intravenous iron to cancer patients, as an adjuvant to erythropoiesis-stimulating agents, for correcting chemotherapy-induced anemia. - Preoperative administration of erythropoiesis-stimulating agents to anaemic, orthopaedic surgical patients expected to have moderate blood losses.

Grade 1B recommendations - The administration of intravenous iron to patients with moderate post-partum anemia or inflammatory bowel disease associated anemia.

We suggest:

Grade 2A recommendations- Perioperative administration of erythropoiesis-stimulating agents to patients undergoing cardiac or gastrointestinal cancer surgery.

Grade 2B recommendations - Preoperative oral iron administration in patients undergoing orthopaedic or colorectal cancer surgery. - Perioperative intravenous iron administration to anaemic patients scheduled for orthopaedic, gynaecological or gastrointestinal surgery. - The administration of intravenous iron, without erythropoiesis-stimulating agents, for treating radiotherapy- or chemotherapy-induced anemia in cancer patients.

Grade 2C recommendations - Postoperative intravenous iron administration for treating postoperative anemia after cardiac, obstetrics and gynaecological or orthopaedic surgical procedures.

Grade 2C recommendations - Postoperative intravenous iron administration for treating postoperative anemia after cardiac, obstetrics and gynaecological or orthopaedic surgical procedures.

We do not recommend:

- The administration of erythropoiesis-stimulating agents to critically ill patients who do not have a previous indication for this therapy. - The administration of oral iron in the postoperative period or in critically ill patients.

Figure 1. Graphical representation for hematochemical parameters of all patients at the end of the three different treatment periods (iv1, os, iv2). (A) Hemoglobin variations during the study (Hb). (B) Transferrin Saturation (TSAT). (C) C-reactive protein (CRP). D: Erythropoietin weekly consumption (Epo).

Figure 1. The histogram explains the efficacy of Sideral^® Forte showing a mean increase of Hb levels of 1.26 g/dl (9.96–11.22 g/dl, p = 0.0309), ferritin levels of 49.946 ng/mL (42.839–92.785 ng/ml, p = 0.2105), of sO₂ of 1.1% (95.2–96.3%, p = 0.3365) and a mean decrease of HR of −2 (85.4–83,4 HR, p = 0.3843).

Table 1. Quality of Life FACT Questionnaire- An Version 04 Modified Fatigue Scale (normal range: 0–28).

		Not at all	A little bit	Somewhat	Quite a bit	Very much
HI7	I feel fatigued	0	1	2	3	4
HI12	I feel weak all over	0	1	2	3	4
An1	I feel listless (“washed out”)	0	1	2	3	4
An2	I feel tired	0	1	2	3	4
An10	I get headaches	0	1	2	3	4
An6	I have trouble walking	0	1	2	3	4
An7	I am able to do my usual activities	0	1	2	3	4

Figure 2. The histogram shows an improvement of the quality of life after 8 weeks of treatment with Sideral^® Forte (20.4–11.6, p = 0.0088).

Table 1. Women aged 27–41 years (n = 4).

	T0	T1	T2	T3
Hb (g/dl)	9.3	9.9	10.3	10.6
Serum Iron (μg/dl)	27	47	58	62
Ferritin (ng/ml)	10	31	69	76
TSAT (%)	18	22	26	34

Table 2. Men aged 31–45 years (n = 5).

	T0	T1	T2	T3
Hb (g/dl)	9.4	10.1	10.5	10.9
Serum Iron (μg/dl)	28.0	51.0	62.0	74.0
Ferritin (ng/ml)	10.0	36.0	76.0	83.0
TSAT (%)	19	24	30	35

Table 3. Both sexes patients aged 27–45 years (n = 9).

	T0	T1	T2	T3
Hb (g/dl)	9.35	10.0	10.4	10.8
Serum Iron (μg/dl)	27.5	49.0	60.0	68.0
Ferritin (ng/ml)	10.0	33.5	72.5	79.5
TSAT (%)	18	23	28	34

Table 1. Anthropometric measure in recruited patients.

	T0	T1	T2
Patients	34	32	28
m/f	8/25	7/24	7/21
Age (years)	46.3 ± 11.6
BMI (kg/m^2)	27.9 ± 3.1	29.8 ± 4.0	29.5 ± 3.7
ø Waist (cm)	95.3 ± 2.3	95.0 ± 3.7	95.1 ± 3.9

Table 2. Anthropometric, hematologic measures and autoimmunity response in CD patients.

	T0	T1	T2
Patients	6	6	5
m/f	1/5	1/5	1/4
BMI (kg/m^2)	26.3 ± 3.1	28.8 ± 4.0	28.1 ± 3.7
ø Waist (cm)	95.3 ± 2.3	95.0 ± 3.7	93.1 ± 3.9
Anemia (years)	9 ± 4
Hb (g/dl)	8.8 ± 2.5	9.8 ± 1.9^§	11.5 ± 1.4^§
MCV	69.6 ± 7.1	72.3 ± 7.0*	73.9 ± 6.3
Ferritin (ng/ml)	13 ± 10	18 ± 7*	23 ± 10^‡
Fe^++ (mcg/ml)	28 ± 17	31 ± 15*	46 ± 11^§
TSH	3.2 ± 1.8	2.7 ± 1.5*	2.6 ± 1.4
fT4	12.3 ± 3.1	13.1 ± 2.8	13.2 ± 2.5
TPO Ab	123 ± 19	111 ± 21	96 ± 16
hTg Ab	187 ± 28	164 ± 31	161 ± 26
TRAb	5 ± 3	4 ± 3	5 ± 2

*p <0,05

^‡p <0.001

^§p <0.0001

Table 3. Anthropometric, hematologic measures and autoimmunity response in NCSG patients.

	T0	T1	T2
Patients	28	24	22
m/f	6/22	5/19	5/17
BMI (kg/m^2)	26.2 ± 3.3	27.0 ± 3.5	26.9 ± 3.4
ø Waist (cm)	92.3 ± 3.1	93.5 ± 3.8	91.9 ± 3. 2
Anemia (years)	7 ± 3
Hb (g/dl)	9.7 ± 1.9	10.6 ± 2.0*	12.5 ± 1.7^§
MCV	73.3 ± 6.9	75.1 ± 5.8	81.6 ± 6.1
Ferritin (ng/ml)	18 ± 10	23 ± 8*	29 ± 7*
Fe^++ (mcg/ml)	25 ± 13	37 ± 12^‡	52 ± 15^§
TSH	3.5 ± 1.4	2.4 ± 1.9^‡	2.2 ± 1.5
fT4	11.7 ± 2.8	12.8 ± 2.8	13.6 ± 2.6
TPO Ab	149 ± 21	128 ± 33	123 ± 29
hTg Ab	131 ± 33	134 ± 26	131 ± 24
TRAb	4 ± 3	3 ± 3	3 ± 2

*p <0.05

^‡p <0.001

^§p <0.0001

Table 4. Liposomal iron supplementation in NCSG patients.

		T1		T2
Marsh type	m/f	Hb (g/dl)	Ferritin (ng/ml)	Hb (g/dl)	Ferritin (ng/ml)
1	3/9	10.2 ± 1.2	18 ± 2	13.4 ± 0.5^‡	27 ± 2^‡
2	3/13	11.1 ± 0.4	16 ± 5	12.0 ± 1.1*	24 ± 5*

*p <0.05 vs T1

^‡p <0.001 vs T1

Table 1. Characteristics of analysed patients.

Sex n/21 (%) Male Female	13/21 (62%) 8/21 (38%)	Only 1 in childbearing age
Medium age	63 years (34–77)
Disease (n)	DLBCL (5); Follicular Lymphoma (4); Low Grade NHL (3); T-cell lymphoma (2); Hodgkin Lymphoma (6); Hairy Cell Leukemia (1)
Medium Hb level (basal)	10.1 ± 1.8 g/dl
Medium Hb level (start EPO)	9.2 ± 0.9 g/dl
Medium Hb level (week 4)	10.8 ± 1.7 g/dl
Medium Hb level (week 8)	10.9 ± 2 g/dl
Adverse events (related to iron somministration, any grade) (%)	1/21 (4%)	Dyspepsia
Bone marrow infiltration (%)	12/21 (57%)
Blood transfusion requirement (%)	8/21 (38%)	5/8 (62%) with bone marrow infiltration Medium age 66 years
Medium number of RBC transfusion	2 Units
Transferrin saturation <20% (%)	7/12 (58%) (we do not have data for 9/21 patients)	6/7 normal or elevated ferritin level
Medium increase of Hb from basal to week 8	0.98 ± 2 g/dl
Medium increase of Hb from start EPO to week 8	1.73 ± 2 g/dl

Table 1. Characteristics of analysed patient.

Total N°	Avg. age	M/F	Avg. Hb (g/dl)	Avg. Sideremia (mcg/dl)	CIRS Severity/ comorbidity	Drugs N°	Cpr N°	Side effects	Adherence
20	76.8	14/7	10.2	31.4	3.23/4.75	4	7.75	1.00%	95.00%

Table 1. Characteristics of analysed patients.

Sex n/21 (%) Male Female	13/21 (62%) 8/21 (38%)	Only 1 in childbearing age
Medium age	63 years (34–77)
Disease (n)	DLBCL (5); Follicular Lymphoma (4); Low Grade NHL (3); T-cell lymphoma (2); Hodgkin Lymphoma (6); Hairy Cell Leukemia (1)
Medium Hb level (basal)	10.1 ± 1.8 g/dl
Medium Hb level (start EPO)	9.2 ± 0.9 g/dl
Medium Hb level (week 4)	10.8 ± 1.7 g/dl
Medium Hb level (week 8)	10.9 ± 2 g/dl
Adverse events (related to iron somministration, any grade) (%)	1/21 (4%)	Dyspepsia
Bone marrow infiltration (%)	12/21 (57%)
Blood transfusion requirement (%)	8/21 (38%)	5/8 (62%) with bone marrow infiltration Medium age 66 years
Medium number of RBC transfusion	2 Units
Transferrin saturation <20% (%)	7/12 (58%) (we do not have data for 9/21 patients)	6/7 normal or elevated ferritin level
Medium increase of Hb from basal to week 8	0.98 ± 2 g/dl
Medium increase of Hb from start EPO to week 8	1.73 ± 2 g/dl

   

Table 1. Type of gastrointrestinal disease considered with number of patients.

Gastrointestinal diseases (type)	Number of patients	Age				Sex
		<2 Years	>2–6 Years	>6–10 years	>10 Years	M	F
HP infection	6	-	-	-	6	1	5
HP infection + Celiac disease	1	-	1	-	-	1
Gastritis	2	-	-	-	2	2	--
Celiac disease	3	1	1	1	-	2	1
Gastro-esophageal reflux disease	2	1	-	-	1	1	1
Meckel’s diverticulum	1	-	1	-	-	-	1
Food intolerances	15	4	8	2	1	12	3

Figure 1. (A) Hemoglobin levels according to age. No statistical difference was found between the different age groups. (B) MCV values according to age. MCV values were significantly lower in children aged >2-6 years and in those older than 10 years. (C) Ferritin values according to the age. Ferritin values were significantly lower in children older than 10 years.

Figure 1. Average Hb g/dl improvement.

Figure 2. Response Hb(t₀)/Hb(t₁).

Group A  

Patient ID	Gender	Age	Hb (t0)	Hb (t0)	Days	ΔHb
12	F	25	11	11.3	20	0.6
19	F	36	12	13.2	20	1.4

Group B  

Patient ID	Gender	Age	Hb (t0)	Hb (t1)	Days	ΔHb
1	F	36	12	13.1	40	1.6
2	M	95	8.1	9.6	40	1.5
3	F	91	8.8	11.9	40	3.1
4	F	19	11	11.7	40	1.2
5	F	45	9	12.3	40	3.3
11	F	41	12	12.5	40	0.7
15	F	77	12	13.1	40	1.5
16	F	89	10	11	40	0.6

Group C  

Patient ID	Gender	Age	Hb (t0)	Hb (t0)	Days	ΔHb
6	M	72	9.7	13	60	3.3
7	F	51	7.8	13.3	60	5.5
10	F	73	10	11.2	60	1.2
13	M	77	12	12	60	0.4
17	M	19	12	12.6	60	1
18	M	90	12	13	60	1.2
20	F	48	11	13.2	60	2.3
23	F	27	12	12.4	60	0.7

Lindgren S, Wikman O, Befrits R, et al. Intravenous iron sucrose is superior to oral iron sulphate for correcting anaemia and restoring iron stores in IBD patients: A randomized, controlled, evaluator-blind, multicentre study. Scand J Gastroenterol 2009;44:838-45.

 PubMed Web of Science ®Google Scholar

Evstatiev R, Marteau P, Iqbal T, et al. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology 2011;141:846-53.e1-2.

 PubMed Web of Science ®Google Scholar

Kulnigg S, Stoinov S, Simanenkov V, et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol 2008;103:1182-92.

 PubMed Web of Science ®Google Scholar

Reinisch W, Staun M, Tandon RK, et al. A randomized, open-label, non-inferiority study of intravenous iron isomaltoside 1,000 (Monofer) compared with oral iron for treatment of anemia in IBD (PROCEED). Am J Gastroenterol 2013;108:1877-88.

 PubMed Web of Science ®Google Scholar

Khalil A, Goodhand JR, Wahed M, et al. Efficacy and tolerability of intravenous iron dextran and oral iron in inflammatory bowel disease: a case-matched study in clinical practice. Eur J Gastroenterol Hepatol 2011;23:1029-35.

 PubMed Web of Science ®Google Scholar

Calvet X, Ruíz MÀ, Dosal A, et al. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose for the ambulatory treatment of severe iron deficiency. PLOS One 2012;7:e45604.

 PubMed Web of Science ®Google Scholar