Treatment of Anemia of Chronic Disease With True Iron Deficiency in Pregnancy
Phase: PHASE4
Conditions: Anemia
Sponsor: University of Zurich

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Treatment of anemia of chronic disease with true iron deficiency in pregnancy  
 
 
31.10.2017 
Treatment of anemia of chronic disease with true iron deficiency in 
pregnancy 
 
Gabriela AMSTAD BENCAIOVA, Alexander KRAFFT, Roland ZIMMERMANN, Tilo 
BURKHARDT 
Department of Obstetrics and Gynecology 
University Hospital of Zurich 
Frauenklinikstrasse 10 
CH-8091 Zurich 
SWITZERLAND 
Phone: 
+41 44 255 51 92 
Email:  
tilo.burkhardt@usz.ch 
 
 
 

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Treatment of anemia of chronic disease with true iron deficiency in pregnancy  
 
 
31.10.2017 
Study population and criteria 
Fifty anemic pregnant women with moderate anemia were prospectively observed and treated 
in the Anemia clinic at the Department of Obstetrics, University Hospital Zurich.  All patients 
had singleton pregnancies.  All pregnant women fulfilled criteria of moderate iron deficiency 
anemia defined as hemoglobin between 8.0 and 9.9 g/dl and serum ferritin <15 µg/l. In all 
women, the analyses of a blood count, iron status, erythropoietin, cross reactive protein (CRP), 
folic acid and vitamin B12 were conducted.  
Primary endpoint was the assessment and comparison of the efficacy of anemia treatment in 
pregnant women with iron deficiency anemia and anemia of chronic disease with true iron 
deficiency.  
Secondary endpoint was the target hemoglobin ≥10.5 g/dl.  
Exclusion criteria were anemia of other etiology (i.e. vitamin B12 deficiency, folic acid 
deficiency, hemoglobinopathy etc.), liver or kidney disease, and multiples.  Women with mean 
corpuscular hemoglobin (MCH) ≤25 pg, mean corpuscular volume (MCV) ≤75 fl; and 
percentage of microcytic erythrocytes (MRC) ≥3% were tested for hemoglobinopathies. 
Flow cytometry was used to determine the total iron demand of erythropoiesis by measuring 
HRC, CHr, and RDW. Iron deficiency anemia is defined as anemia with depleted iron stores 
and with elevated levels of HRC >2.5%, decreased CHr <28 pg and elevated RDW >15%. In 
combination with the indicators of erythropoiesis (hemoglobin, red blood cells and hematocrit) 
as well as the indicators of iron household (serum ferritin and transferrin saturation), we 
identified anemia of chronic disease with reduced iron stores but with normal level of 
hypochromic erythrocytes (HRC <2.5%), normal reticulocyte hemoglobin content (CHr >28 
pg)), normal red blood cell distribution width (RDW <15%) and low serum EPO levels for the 
grade of anemia (serum EPO <50 U/l by Hb <10 g/dl). 

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Treatment of anemia of chronic disease with true iron deficiency in pregnancy  
 
 
31.10.2017 
Laboratory assessment 
Hb, red blood cells (RBC), hematocrit (HCT), MCV, MRC, HRC, RDW, CHr were measured 
using an ADVIA® hematology analyser system (Bayer Diagnostics, Leverkusen, Germany). 
MCH was automatically calculated from Hb and RBC. Iron status was assessed by 
chemiluminescence–immunoassay (ACS 190; Ciba/Corning Diagnostic Corp., Cleveland, 
OH) of serum ferritin, iron and transferrin. Transferrin saturation was calculated as 100 x iron/2 
x transferrin. Radioimmunoassay was performed to determine vitamin B12, folic acid and the 
levels of serum EPO. CRP was assessed through immunoturbidimetry.  The hematological 
parameters were checked twice a week in the anemia clinic and iron status once a week. 
 
Therapy protocol 
According to hemoglobin level at the start of the therapy, the women were either treated with 
intravenous iron and rhEPO or with intravenous iron only twice weekly as described elsewhere.  
Patients with an Hb level between 9.0 and 9.9 g/dl (33 patients) received 200 mg iron sucrose 
(VENOFER®, Vifor Int., St. Gallen, Switzerland) intravenously twice weekly. If response to 
therapy was poor (i.e. Hb increase <0.7 g/dl) after 2 weeks (13 patients), patients additionally 
received rhEPO (10,000 U EPREX®, Janssen-Cilag, Baar, Switzerland). This cut-off for 
adequate primary response we choose on the basis of our previous experience.  Patients with 
an Hb between 8.0 and 8.9 g/dl (17 patients) received iron sucrose (Venofer) and rhEPO 
(Eprex) twice weekly from the start of therapy.  
Sufficient overall response to therapy (the difference of baseline hemoglobin and after therapy) 
was defined as Hb increase >1.0 g/dl. The maximum total iron dose was 1,600 mg, therefore 
therapy was stopped if the maximal iron sucrose dose was administered, or target Hb > 10.5 
g/dl was achieved. 

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Treatment of anemia of chronic disease with true iron deficiency in pregnancy  
 
 
31.10.2017 
Side-effects (hypotensive and hypertensive response, allergic reaction, thromboembolic 
complications) were registered. 
Statistical analysis 
All statistical analyses were performed using the statistic program STATA 8 (Stata Corporation 
College Station, TX). P<0.05 was considered statistically significant. Baseline characteristics 
were compared using Mann-Whitney and Chi-square tests when appropriate.