1. The Women’s Health strategy: A portfolio approach
Anna Mezzacasa
Global Medical Affairs
Medical Lead Women’s Health, Patient Blood Management
& Life Cycle Management

2. Prevalence (proportion)
Prevalence of anaemia and iron deficiency anaemia
Iron-deficiency is the global #1 cause of anaemia and also #1 in many regions
Most causes are more common amongst females
Malaria
Hookworm disease
Schistosomiasis
Other infectious diseases
Other neglected tropical diseases
Maternal haemorrhage
Uterine fibroids
Other gynaecological diseases
Sickle cell disorders
Thalassaemias
G6PD deficiency
Other haemoglobinopathies and haemolytic anaemias
Iron-deficiency anaemia
Other endocrine, nutritional, blood and immune disorders
Gastritis and duodenitis
Peptic ulcer disease
Chronic kidney disease (due to diabetes mellitus)
Chronic kidney disease (due to hypertension)
Chronic kidney disease (unspecified)
0.3
0.2
Prevalence (proportion)
0.1
0.0
1990
2013
1990
2013
Females
Year
Males
GBD 2013 Mortality and Causes of Death Collaborators. Lancet 2015;385:117–171

3. ID/IDA is easy to diagnose, easy to treat, still easy to ignore
Kassebaum NJ et al. Blood, 2014;123:

4. Statements from World Health Organisation
“All women of reproductive age are at risk of iron deficiency. ”
“… IDA has been associated with increased risks of low birth weight, prematurity and maternal morbidity.”
WHO. Worldwide prevalence of anaemia,1993–
WHO. Guideline: Daily iron and folic acid supplementation in pregnant women
WHO. Micronutrient deficiencies

5. The gender gap for ID/IDA burden is widening
Prevalence (per 100,000 population)
Total anaemia prevalence, global by age
80,000
Males, 1990
Females, 1990
Males, 2010
Females, 2010
60,000
40,000
Results from a systematic analysis of global anaemia up to 2010 have shown that the magnitude of the gender gap in anaemia burden has widened since 1990
In 2010, women demonstrated higher prevalence and severity of anaemia than men in generally all affected regions of the world (notably, Central Asia [43.2% versus 22.8%] and Asia Pacific [19.4% versus 10%]) and throughout adulthood
Although anaemia prevalence rates in 2010 have declined since 1990, estimates show continued higher frequency of the disease in women than men
Reference:
Kassebaum NJ, et al. Blood 2014;123:
20,000 20 40 60 80
Age
Kassebaum NJ et al. Blood 2014;123:

6. Importance of iron for functioning and survival across all levels of complexity of living structures
Iron is critical for optimal functioning and survival
Iron deficiency results in:
Mitochondrial dysfunction
Deranged activity of enzymes
Abnormal transport and structural proteins
Apoptosis
Cells
Tissues
Tissue remodelling
Impaired organ efficacy
Organs
SOURCE: Slide 66 e-learning module 2
Body
Impaired exercise capacity
Reduced work efficacy
Impaired cognitive performance and behaviour
Increased morbidity and mortality
Population
Adapted from Jankowska EA, et al. Eur Heart J 2013;34:816–26.

7. Fatigue – a common burden of ID/IDA
A multidimensional condition1–3
Physical exhaustion, lack of energy
Mental tiredness, cognitive impairment
A substantial public health burden
Affects 14–33% of general practitioner patients1,4,5
Women are more often affected by fatigue than men6–8
Fatigue is often associated with anaemia9
Fatigue encompasses a myriad of symptoms ranging between physical exhaustion to stress and emotional problems1,2
As a predominant presenting symptom among patients seeking treatment in general practice, fatigue is associated with prevalence rates of 14–33% and occurs twice as often in women than men1,3–6
The association between fatigue and IDA, both highly prevalent among women, is gaining recognition7
ID in the absence of anaemia is a significant nutritional disorder commonly observed in industrialised countries, especially among children, menstruating women and pregnant women; low-energy, vegetarian or vegan diets may render such groups at particular high risk of ID8,9
References:
1. Cathebras PJ et al. J Gen Intern Med 1992;7:
2. Radbruch L et al. J Pain Symptom Manage 2003;25:
3. Bates DW et al. Arch Intern Med 1993;153:
4. Kroenke K et al. Arch Intern Med 1990;150:
5. Morrison JD. J Fam Pract 1980;10:
6. Ridsdale L et al. BMJ 1993;307:
7. Krayenbuehl PA et al. Blood 2011;118:
8. Hercberg S et al. Public Health Nutr 2001;4:
9. Galan P et al. Eur J Clin Nutr 1998;52:
1. Cathebras et al. J Gen Intern Med 1992;7:276–286; 2. Radbruch et al. J Pain Symptom Manage 2003;25:449–458; 3. Brownlie et al. Am J Clin Nutr 2004;79:437–443; 4. Bates et al. Arch Intern Med 1993;153:2759–2765; 5. Kroenke et al. Arch Intern Med 1990;150:1685–1689; 6. Ridsdale et al. Br Med J 1993;307:103–106; 7. Morrison. J Fam Pract 1980;10:795–801; 8. Krayenbuehl et al. Blood 2011;118:3222–3227; 9. Hercberg et al. Clin Drug Invest 2000;19(Suppl 1):1–7

8. IDA – a global leader in disability3 13 $ + =
IDA is the third leading cause of disability1,2
ID ranks as the thirteenth leading risk factor of DALYs2
The high prevalence of IDA has important adverse economic consequences3,4
According to 2010 values (Global Burden of Disease study), ID and IDA rank high (13th and 15th of the top 25, respectively) among the leading causes of disability in men and women worldwide1
From a worldwide perspective, IDA is attributed to a significant proportion of years lived with disability (YLDs) due to communicable, maternal, neonatal and nutritional disorders, accounting for 5.5% of all YLDs2
The economic burden imposed by IDA is substantial, largely reflecting the significant cost consequences of decreased productivity3,4
References:
Murray CJL et al. NEJM 2013;369:
Vos T et al. Lancet 2012;380:
3. Hunt JM. J Nutr 2002;132:794S-801S.
4. Horton S, Ross J. Food Policy 2003;28:51-75.
“Iron deficiency and anaemia reduce the work capacity of individuals and entire populations, bringing serious economic consequences and obstacles to national development”5
1. Vos T et al. Lancet 2012;380:2163–96; 2. Murray CJ et al. NEJM 2013;369:448–57; 3. Hunt JM. J Nutr 2002;132:794S–801S; 4. Horton S & Ross J. Food Policy 2003;28:51–75; 5. WHO. Micronutrient deficiencies

9. Women’s Health is not one therapeutic area
HMB
Up to 30%
of women
suffering
from HMB
are iron
deficient
Pregnancy
Postpartum
40%
of pregnant women
are iron deficient
25%
of women
a week after birth
are iron deficient
Total iron requirement increases throughout pregnancy, from ~0.8 mg/day in the first trimester to 4–5 mg/day in the second trimester and >6 mg/day in the third trimester
In the first trimester, the demand for iron declines because menstruation ceases
In the second trimester, iron requirements escalate due to major haematologic changes resulting from increased oxygen consumption by the mother and foetus
In the third trimester, total iron requirement continues to rise steadily in proportion with the growing foetus
To meet the demand of the expansion in red blood cell mass that begins in the middle of the second trimester, iron needs may reach 10 mg/day in the last 6–8 weeks of pregnancy
Reference:
Bothwell TH. Am J Clin Nutr 2000;72:257S–264S
Fatigue/exhaustion is a common symptom
> 30% of women present with fatigue symptoms in the general practice
*Woman weighing 55 kg at the beginning of her pregnancy
Bothwell TH. Am J Clin Nutr 2000;72:257S−64S 9 9

10. Prevalence of anaemia* (±95% CI) Non- pregnant women 15–50 years
Greatest absolute number of individuals affected by anaemia: non-pregnant women
24.8% global prevalence of anaemia 25 50
Prevalence of anaemia* (±95% CI)
47.4
Children <5 years
25.4
Children ≥5 years
30.2
41.8
Pregnant women
12.7
23.9
Men
15–60 years
Elderly
>60 years
Non- pregnant women 15–50 years
When categorised by patient group, the worldwide prevalence of anaemia (defined by the World Health Organization [WHO] as a Hb level <11.0 g/dL) approaches 50% for children younger than 5 years of age (47.4%) and for pregnant women (41.8%).1
However, the category with the greatest absolute number of individuals affected by anaemia is non-pregnant women (468 million women).1
The prevalence of anaemia in pregnant women is classified as a moderate (>20–39.9% prevalence) or severe (≥40%) public health problem in >80% of countries included in the WHO Global Database.1
The leading cause of anaemia in elderly patients is chronic disease.2 Vitamin B12 deficiency and folate deficiency are among other causes of anaemia in the elderly.2
Reference:
WHO. Worldwide prevalence of anaemia, 1993–
Beghe C, Wilson A, Ershler WB. Am J Med 2004;116 Suppl 7A:3S‒10S.
*Including industrialized countries. Children (6–59.9 months) Hb <11 g/dL; children (5–11.99 years) Hb <11.5 g/dL; children (12–14.99 years) Hb <12 g/dL; pregnant women Hb <11 g/dL; women Hb <12 g/dL; men Hb <13 g/dL
WHO. Worldwide prevalence of anaemia,1993–
CI, confidence interval

11. Clinical definition of HMB
For clinical purposes, HMB should be defined as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms
HMB should be recognized as having a major impact on a woman’s quality of life
Any interventions should aim to improve quality-of-life measures
NICE guideline. Heavy menstrual bleeding

12. Heavy menstrual bleeding (HMB) is the leading cause of ID/IDA treatment in women
Patients (%)
ID with anaemia
ID without anaemia
HMB and pregnancy account for more than half of the cases of iron deficiency and anaemia
Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss (i.e. greater than 80 mL per menstrual cycle)1
In a study conducted among Swiss general practitioners, gynaecologists and gastroenterologists, HMB was the underlying cause in almost half of patients treated for ID/IDA in routine practice2
A US claims database analysis reported a high prevalence of anaemia (>25%) among more than 300,000 women hospitalised for gynaecologic conditions associated with HMB3
HMB invariably affects physical, emotional, social and material quality of life of sufferers4
References:
Marret H et al. Eur J Obstet Gynecol Reprod Biol 2010;152:
Beglinger C, Breymann C. Schweiz Med Forum 2010;10:1-6.
Morrison J et al. J Reprod Med 2008;53:
Fraser IS et al. Exp Rev Obstet & Gynecol 2009;4:
In Swiss registry analysis, 67% of subjects with a blood loss >80 mL presented with an Hb <12 g/dL
Beglinger & Breymann. Schweiz Med Forum 2010;10:1–6

13. HMB increases the risk of anaemia
20% of menstruating women are anaemic
67% of women with a blood loss of >80 mL presented with an Hb <12 g/dL
>25% of women hospitalized for gynaecological conditions associated with HMB have anaemia
NICE guideline. Heavy menstrual bleeding
Hallberg L et al. Acta Obstet Gynecol Scand 1966;45:320–351
Vanella L et al. Aliment Pharmacol Ther 2008;28:422–430
de Benoist B et al. World Health Organization 2008
McLean F et al. Public Health Nutrition 2008;12:444–454
Van Wyck DB et al. Transfusion 2009;49:2719–2728
Morrison J et al. J Reprod Med 2008;53:323–330

14. HMB increases the risk of anaemia and therefore blood transfusions
HMB and blood transfusions
Anaemic patients were more likely to have a blood transfusion than those who were not anaemic (24% vs 0.7%, P<0.0001)
Increased risk of transfusion prior to surgery
Morrison et al., 2008 conducted a study to estimate the prevalence and impact of anaemia in women hospitalised for gynaecologic conditions associated with HMB. The Healthcare Cost and Utilization Project's 2003 Nationwide Inpatient Sample, was queried using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to identify and group women with gynaecologic diagnoses associated with heavy uterine bleeding into 2 categories: those with or without anaemia.
More than 25% of the estimated 300,589 women in the study had a diagnosis of anaemia. Compared to patients without a diagnosis of anaemia, those with an anaemia diagnosis were more likely to have a blood transfusion (24% vs. 0.7%, p<0.0001). It was concluded that anaemia and blood transfusions are common in women hospitalized for gynaecologic conditions associated with HMB. Greater patient and provider awareness of the prevalence and burden associated with anaemia may increase opportunities to reduce blood transfusions and improve general health status and quality of life in this patient population.
Reference:
Morrison J, Patel ST, Watson W, Zaidi QR, Mangione A, Goss TF. Assessment of the prevalence and impact of anemia on women hospitalized for gynecologic conditions associated with heavy uterine bleeding. J Reprod Med. 2008;53(5):
Van Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JA, Goodnough LT. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion
McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. World wide prevalence of anaemia, WHO Vitamin and Mineral Information System, Public Health Nutrition. 2008; 12(4):
Vannella L, Aloe Spiriti MA, Cozza G, Tardella L, Monarca B, Cuteri A, Moscarini M, Delle Fave G, Annibale B. Benefit of concomitant gastrointestinal and gynaecological evaluation in premenopausal women with iron deficiency anaemia. Aliment Pharmacol Ther. 2008;28(4):
Lyseng-Williamson KA, Keating GM. Ferric carboxymaltose: a review of its use in iron-deficiency anaemia. Drugs. 2009;69(6):
de Benoist B, McLean E, Egli I, Cogswell, M. Worldwide prevalence of anaemia : WHO Global Database. Geneva: World Health Organization, 2008.
Hallberg L, Hogdahl AM, Nilsson L, Rybo G. Menstrual blood loss–-a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand. 1966;45:320–51.
NICE. Clinical Guidelines, Hallberg L et al. Acta Obstet Gynecol Scand 1966;45:320–351 Vannella L et al. Aliment Pharmacol Ther 2008;28:422–430; de Benoist B et al. World Health Organization, McLean E et al. Public Health Nutrition 2008;12:444–454; Van Wyck DB et al. Transfusion 2009;49:2719–2728 Morrison J et al. J Reprod Med 2008;53:323–330 14

15. High risk of iron deficiency in pregnancy
Estimated daily iron requirement increases ~10-fold from first to third trimester of pregnancy*
~40% women were iron deficient before pregnancy3
Total iron requirement increases throughout pregnancy, from ~0.8 mg/day in the first trimester to 4–5 mg/day in the second trimester and >6 mg/day in the third trimester
In the first trimester, the demand for iron declines because menstruation ceases
In the second trimester, iron requirements escalate due to major haematologic changes resulting from increased oxygen consumption by the mother and foetus
In the third trimester, total iron requirement continues to rise steadily in proportion with the growing foetus
To meet the demand of the expansion in red blood cell mass that begins in the middle of the second trimester, iron needs may reach 10 mg/day in the last 6–8 weeks of pregnancy
Reference:
Bothwell TH. Am J Clin Nutr 2000;72:257S–264S
Bothwell TH. Am J Clin Nutr 2000;72:257S–264S
Hallberg L. In: Foman SJ, Zlotkin S, eds. Nutritional anemias. New York: Raven Press, 1992:13–28
Milman N. Ann Hematol 2008;87:949–959
*Woman weighing 55 kg at the beginning of her pregnancy 15 15

16. Therefore critical to ensure the pregnant mother
Iron deficiency at birth has a long term negative impact on cognitive performance
Therefore critical to ensure the pregnant mother
has sufficient iron stores before delivery
Cognitive scores to age 19 in 185 individuals
with or without chronic iron deficiency in infancy
125
115
p=0.01
105
Middle SES, good iron status
Middle SES, chronic iron deficiency 95
Cognitive scores
p=0.003
Low SES, good iron status
Low SES, chronic iron deficiency
The Valencia Infant Anaemia Cohort [VIAC] prospective study tested the potential for development of ID in 62 neonates born to mothers with ferropenic anaemia
After 1 year of follow-up, a higher proportion of infants born to iron-deficient mothers exhibited evidence of ID (14 of 47; 29.8%) when compared with infants born to mothers with normal iron status (4 of 66; 6.1%)
These results translated to a highly significant association between IDA status in the mother and development of ID in the infant in the first year of life (odds ratio of 6.57; 95% CI 1.8, 26.0; P=0.0007)
Adjustment for confounding effects of socio-economic factors, feeding practices and other factors potentially associated with iron status did not affect the association
Reference:
Colomer J et al. Paediatr Perinat Epidemiol 1990;4:196–204 85 75
SES = Socio-economical status 1 3 5 7 9 11 13 15 17 19
Age (years)
Lozoff B et al. Arch Pediatr Adolesc Med 2006;160:1108–1113 16

17. Iron requirements are high during pregnancy and postpartum
Erythrocyte mass
Blood loss at delivery
Gross total
Newborn (weight 3.5 kg)
Placenta + umbilical cord
Obligate loss*
Erythrocyte mass PP
Amenorrhoea
Net iron loss:
450
160
200
230
270
1240
400
600
800
1000
1200
Iron (mg)
1400
~630 90
400 mL of blood loss
During pregnancy, it is estimated that a woman (55 kg in weight) will require 1,240 mg of iron in total1
Iron loss is associated with expansion of the red blood cell mass, blood loss at delivery, obligate loss, and iron content of the placenta/umbilical cord and newborn1,2
450 mg of iron is recycled back to body iron stores following the postpartum contraction of red blood cell mass and a further 160 mg is gained by the absence of menstruation during pregnancy1,2
Therefore, the net iron requirement during pregnancy is ~630 mg1
References:
1. Milman N. Ann Hematol 2006;85:559–565
2. Bothwell TH. Am J Clin Nutr 2000;72:257S–264S
*0.8 mg x 290 days
Milman N. Ann Hematol 2006;85:559–65
PP, postpartum

18. Risk of obstetric haemorrhage
Pre-existing IDA does place women at greater risk of haemorrhage during childbirth
Risk of obstetric haemorrhage
In Senegal and Mali, severe chronic anaemia was significantly associated with risk of PPH maternal mortality (all delivery methods) Tort J et al. BMC Pregnancy Childbirth 2015;15:235
Women in Ghana with moderate–severe anaemia (Hb <10 g/dL) undergoing vaginal deliveries
“For every unit increase in Hb, the odds of developing primary PPH decreased times (95% CI 0.46, 0.73).” Owiredu K L et al. BMC Preg Childbirth 2016;16:17
OR 6.65 (3.77, 11.74)
OR 3.14 (1.21, 8.14)
Women in Egypt with antepartum Hb ≤11 mg/dL who underwent vaginal deliveries Prata N et al. BMC Pregnancy Childbirth 2011;11:97
Women in US who underwent vaginal deliveries Wetta L et al. Am J Obstet Gynecol 2013;209:51.e1–6
OR 2.73 (1.43, 5.23)
OR 2.46 (0.92, 6.56)
UK women from ethnic minorities diagnosed with anaemia during their current pregnancy (all delivery methods) Nair M et al. PloS One 2014;9:e95086
UK births (all delivery methods)
Pre-pregnancy anaemia
During pregnancy and Hb <10.5 g/dL
PPH ≥1500 mL
OR 1.31 (0.35, 4.95)
OR 1.27 (0.84, 1.92)
PPH ≥500 mL
OR 0.76 (0.24, 2.43)
OR 1.15 (0.83, 1.60)
Briley a et al. BJOG 2014;121:876–888
OR 1.82 (1.00, 3.32)
OR 0.99 (0.72, 1.35)
Women in rural Uganda with moderate–severe anaemia during pregnancy (all delivery methods) Ononge S et al. Reprod Health 2016;13:38
For PPH ≥500 mL unless otherwise stated

19. 480,000 postpartum maternal deaths/year 1
Maternal mortality ratio per 100,000 live births4
Postpartum haemorrhage1
Sepsis1
Thromboembolism1
Postpartum depression2
Less than 10 deaths per 100,000
10–199 deaths per 100,000
200–499 deaths per 100,000
500–999 deaths per 100,000
Greater than or equal to 1000 deaths per 100,000 Data not available
50–90% are avoidable3
1. Say L et al. Lancet Glob Health 2014;2:e323–33S; 2. CMACE. BJOG 2011;118;s11–203; 3. Saucedo M et al.Obstet Gynecol 2013;122:752–60; 4. WHO Trends in maternal mortality: 1990 to

20. Caesarean section – the rising trend and associated risks
Increased blood loss
Knight M et al. BMC Preg Childbirth 2009;9:55; Stones RW et al. Eur J Obstet Gynecol Reprod Biol 1993;48:15–18

21. Trends in postpartum haemorrhage associated with type of delivery
All pregnancies are at risk of PPH
even if no predisposing factors are present
Deliveries (%)
4.0
Population-based surveillance data from the US
3.5
3.0
2.5
2.0
1.5
Vaginal induced
Caesarean induced
Vaginal not induced
Caesarean not induced
All atony
1.0
0.0
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Year
Callaghan WM et al. Am J Obstet Gynecol 2010;202:353;e1–6

22. Latest data show that caesarean section rates continue to increase globally
The global average rate increased by 12.4% between 1990 and 2014, with an average annual increase of 4.4%
UN region
Europe
World total
Latin America and the Caribbean
North America
Asia
North Africa
Oceania
Africa
Sub-Saharan Africa 50 40 30 20 10
1990
1995
2000
2005
2010
2015
Year
Caesarean section, %
Betrán AP et al. PLoS One 2016;11:e

23. Latest data show that PPH rates are increasing (1)
PPH rates in 818,965 births in New South Wales, Australia
Vaginal births
36% increase
55% increase
Ford JB et al. BMC Pregnancy Childbirth 2015;15:334

24. Latest data show that PPH rates are increasing (2)
PPH rates in 412,093 live and stillbirths in British Columbia, Canada
27% increase
Mehrabadi A et al. BMC Pregnancy Childbirth 2012;12:108

25. Caesarean section and an increasing trend in postpartum haemorrhage
Increased blood loss
Increased risk of postpartum haemorrhage
Knight M et al. BMC Preg Childbirth 2009;9:55; Stones RW et al. Eur J Obstet Gynecol Reprod Biol 1993;48:15–18

26. Rates of obstetric blood product transfusion
Packed cells only Packed cells and platelets or coagulation factors Platelets or coagulation factors only
All births in hospitals in New South Wales, Australia
Increased risk:
Bleeding or platelet disorders
+ VD: RR 7.8, 95% CI 6.9, 8.7
+ CS: RR 8.7, 95% CI 7.6, 9.7
Placenta praevia + CS: RR 5.7, 95% CI 5.1, 6.4
ID + VD RR 7.1, 95% CI 6.2, 8.2
ID + CS: RR 4.7, 95% CI 3.7, 5.8
Transfusion rate per 1000 deliveries 16 14 12 10 8
Increase by 33%, largely associated with haemorrhage 6 4 2
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Year
Patterson JA et al. Obstet Gynecol 2014;123:126–133

27. Blood transfusion and caesarean sections
19-university observational study in the US
Primary caesarean deliveries – multivariable analysis of risk factors for PRBC transfusion
Variable
n (%)
OR for PRBC transfusion (95% CI)
African-American or Hispanic race
12,331 (52.5)
1.3 (1.1, 1.6)
Multiple gestation
1,637 (7.0)
1.7 (1.3, 2.1)
Pre-eclampsia
3,084 (13.1)
1.9 (1.6, 2.3)
Chorioamnionitis
2,387 (10.2)
2.5 (2.0, 3.2)
Placental abruption
807 (3.4)
2.9 (2.2, 3.7)
Mild anaemia (haematocrit 25–29%)
1,615 (7.5)
3.4 (2.8, 4.2)
General anaesthesia
2,836 (12.1)
4.2 (3.5, 5.0)
Eclampsia or HELLP syndrome
353 (1.5)
4.3 (3.1, 6.2)
Placenta previa
506 (2.2)
4.8 (3.5, 6.5)
Severe anaemia (haematocrit <25%)
236 (1.1)
17.0 (12.4, 23.3)
3.2% rate of transfusion
Repeat caesarean deliveries – multivariable analysis of risk factors for PRBC transfusion
Variable
n (%)
OR for PRBC transfusion (95% CI)
Pre-eclampsia
1,925 (5.7)
1.6 (1.2, 2.1)
African-American or Hispanic race
19,038 (56.5)
1.7 (1.4, 2.0)
Race category ‘other’
1,617 (4.8)
2.0 (1.4, 2.9)
Chorioamnionitis
561 (1.7)
2.5 (1.7, 3.8)
Placental abruption
504 (1.5)
2.6 (1.8, 3.7)
Mild anaemia (haematocrit 25–29%)
2,662 (8.4)
3.8 (3.1, 4.6)
General anaesthesia
1,654 (4.9)
7.2 (5.9, 8.7)
Five or more prior caesareans
110 (0.3)
7.6 (4.0, 14.3)
Placenta praevia
394 (1.2)
15.9 (12.0, 21.0)
Severe anaemia (haematocrit <25%)
279 (0.9)
19.9 (14.5, 27.2)
Rouse DJ et al. Obstet Gynecol 2006;108:891
(Erratum in: Obstet Gynecol 2006;108:1556)
OR, odds ratio; PRBC, packed red blood cell transfusion; CI, confidence interval HELLP, the syndrome of haemolysis, elevated liver enzymes, and low platelets

28. ID/IDA treatment recommendations for pregnant women
Hb (g/dL) 8 9 10 11
I.V. iron
Oral iron
Switzerland1
I.V. iron
Oral iron
Germany2
I.V. iron
Oral iron
Asia Pacific3
1st and 2nd trimester: Oral iron
Breymann C. Arch Gynecol Obstet 2010;282:
Beris P. TATM 2007;9:29-30
Bergmann RL. Geburtsh Frauenheilk 2009;69:
Pavord S. Br J Haematol 2012;156:
Breymann C. J Perinat Med 2011;39:
UK4
3rd trimester: I.V. iron
Additional serum ferritin cut-offs and detailed dosing recommendations in the original publications
1. Breymann et al. Arch Gynecol Obstet 2010;282:577–80; 2. Bergmann et al. Geburtsh Frauenhilk 2009;69:682–6;
3. Breymann et al. J Perinat Med 2011;39:113–21; 4. Beris et al. Transfus Altern Transfus Med 2007;9:29–30

29. ID/IDA treatment recommendations for postpartum women
Hb (g/dL) 8 9 10 11
I.V. iron
Oral iron
Switzerland1
I.V. iron
Oral iron
Germany2
I.V. iron
Oral iron
Asia Pacific3
Breymann C. Arch Gynecol Obstet 2010;282:
Beris P. TATM 2007;9:29-30
Bergmann RL. Geburtsh Frauenheilk 2009;69:
Pavord S. Br J Haematol 2012;156:
Breymann C. J Perinat Med 2011;39:
I.V. iron
UK4
Additional serum ferritin cut-offs and detailed dosing recommendations in the original publications
1. Breymann et al. Arch Gynecol Obstet 2010;282:577–80; 2. Bergmann et al. Geburtsh Frauenhilk 2009;69:682–6;
3. Breymann et al. J Perinat Med 2011;39:113–21; 4. Beris et al. Transfus Altern Transfus Med 2007;9:29–30

30. Summary of guidelines – iron supplementation in patients with HMB
HMB should be recognized as having a major impact on a woman’s quality of life
Treatment of the primary cause of HMB
Anaemia is mentioned as a secondary condition1,2
Iron supplementation is recommended,2 although details regarding which form of iron therapy are not addressed
Any interventions should aim to improve quality-of-life measures3
General guidelines on IDA recommend oral iron as first-line therapy and the use of i.v. iron second-line, when oral iron is ineffective or cannot be used
WP Management of HMB. NZ Med J 1999;112:174–7
Marret et al. Eur J Obstet Gynecol Reprod Biol 2010;152:133–7
NICE Guidelines: Heavy Menstrual Bleeding 2007

31. The need to treat ID/IDA in women
Women are particularly vulnerable to ID/IDA at all stages of their life
Iron is essential for energy metabolism, and healthy immune and nervous systems
There is a substantial physical and mental impact of ID/IDA in women
ID/IDA in mothers impacts on the development of their offspring
Treatment of ID/IDA in women is recommended, with pregnant/post-partum women identified as priority target groups for iron supplementation
In non-pregnant women, there is an increased iron need to compensate for blood loss through menstruation, which is largely unmet

32. The negative iron spiral in Women’s Health – and how to reverse it
HMB
Iron treatment
Pregnancy
Ferritin level
Heavy blood loss at birth
HMB
Pregnancy
Heavy blood loss at birth
Iron deficiency (anaemia)

33. Women’s Health is not one therapeutic area
HMB
Up to 30%
of women
suffering
from HMB
are iron
deficient
Pregnancy
Postpartum
40%
of pregnant women
are iron deficient
25%
of women
a week after birth
are iron deficient
Total iron requirement increases throughout pregnancy, from ~0.8 mg/day in the first trimester to 4–5 mg/day in the second trimester and >6 mg/day in the third trimester
In the first trimester, the demand for iron declines because menstruation ceases
In the second trimester, iron requirements escalate due to major haematologic changes resulting from increased oxygen consumption by the mother and foetus
In the third trimester, total iron requirement continues to rise steadily in proportion with the growing foetus
To meet the demand of the expansion in red blood cell mass that begins in the middle of the second trimester, iron needs may reach 10 mg/day in the last 6–8 weeks of pregnancy
Reference:
Bothwell TH. Am J Clin Nutr 2000;72:257S–264S
Fatigue/exhaustion is a common symptom
> 30% of women present with fatigue symptoms in the general practice
*Woman weighing 55 kg at the beginning of her pregnancy
Bothwell TH. Am J Clin Nutr 2000;72:257S−64S 33 33

34. Women’s Health is not one therapeutic area Strategy over time
HCP
Others
General practitioners
Postpartum & Pregnancy
Entry point
OB/Gyn
Sales
Organization
Postpartum & Pregnancy
HMB
Fatigue

35. A portfolio approach to ensure aligned messaging
Ensure the optimal iron treatment by Vifor Pharma’s portfolio to the appropriate patient groups
Make iron therapy available for as many patients as possible

36. Remind health care providers
Iron deficiency anaemia frequently occurs and causes disability
Despite causing so much disability, iron deficiency anaemia does not receive the required attention
Iron deficiency even without anaemia also has a high symptom burden
Assess iron deficiency, not just anaemia
Treat it!

37. ID/IDA in the life course of women
HMB
Pregnancy
Postpartum
Surgery:
Poor outcomes with
ID pre-operatively
LINK: BLOOD LOSS
Greater risk of HMB in older women
LINK: BLOOD LOSS
Impact of ID/IDA on fertility
Increased iron needs

38. Patient Blood Management Program Anna Mezzacasa Global Medical Lead WH, PBM & LCM On behalf of the Patient Blood Management Core Team

39. What is Patient Blood Management?
The timely application of evidence-based medical and surgical concepts designed to maintain haemoglobin concentration, optimize haemostasis and minimize blood loss in an effort to improve patient outcome
The concept of PBM
is not centered on a specific pathology or procedure
is not centered on a specific discipline or sector of medicine
is aimed at managing a resource: "the patient's blood"
It is aimed at shifting attention from the blood component to the patient
17/09/2018

40. Anaemia & Iron Deficiency Independent Risk Factor for Adverse Outcomes
Anaemia independently associated with increased:
morbidity
hospital length of stay
Mortality
likelihood of transfusion (2-9 fold)
Mussallam KM et al. Lancet 2011
Spahn DR. Anesthesiology 2010; 113(2) 1-14
Beattie WS, et al Anesthesiology 2009; 110(3)
Dunne JR, et al J Surg Res 2002; 102:
Shander A. Am J Med 2004; 116(7A) 58S-69S
Courtesy of Prof. A. Shander and Prof. A. Hofmann

41. Blood Loss & Bleeding Independent Risk Factor for Adverse Outcomes
Major blood loss associated with increased
Mortality (3-fold)
Major morbidity (3-fold)
ICU and hospital length of stay
Likelihood of transfusion
Causes
On average 75 – 90% local surgical interruption or vessel interruption
10–25% acquired or congenital coagulopathy
Shander A. Surgery 2007
Ranucci M et al. Ann Thorac Surg 2013; 96:478
Vivacqua et al Ann Thorac Surg 2011
Christensen et al J Thorac Cardiovasc Surg 2009
Spence et al Am J Surg 1990
Stokes, M.E., et al BMC Health Serv Res, 2011
Ye, X., et al BMC Health Serv Res, 2013
Alstrom, U., et al Br J Anaesth, 2012
Blood Loss & Bleeding
Courtesy of Prof. A. Shander and Prof. A. Hofmann

42. Independent risk factor of further worsening the outcome of patients
The default solution to manage peri-operative IDA
is frequently still a Red Blood Cell Transfusion (RBC)
ID(A)
Blood Loss
RBC transfusion  - OR 5.04 (4.12 – 6.17, p< 0.001)
Blood transfusion
Most common procedure performed during hospitalizations in 2011
(12% of stays with a procedure); rate of hospitalizations with blood transfusion more than doubled since 1997.
Carson et al. Cochrane Review 2012/ Salpeter et al. Am J Med 2014/ Rohde at al. JAMA 2014
Likosky DS et al. Ann Thorac Surg 2015/ Shaw et al. Transfusion 2014/ Parsons J et al. Crit Care 2013/ Horvath K et al. Ann Thorac Surg 2013/ Linder et al. BJU Int 2013/ Al-Refaie et al Surgery 2012/ Ferraris V et al. Arch Surg 2012/ Paone G et al. J Thorac Cardiovasc Surg 2012/ Bhaskar B et al. Ann Thorac Surg 2012/ Stone GW et al. Am Heart J 2012/ Xenos et al. Thromb Res 2012/ Ferraris et al. Ann Thorac Surg 2011/ Glance L et al. Anesthesiol 2011/ Ranucci M et al. J Thorac Cardiovas Surg 2011/ Haijar LA et al. JAMA 2010/ Beattie et al. Anesthesiology 2009/ Bernard et al. J Am Coll Surg 2009/ Bursi et al. Eur J Vasc Endovasc Surg 2009/ Chaiwat O et al. Anesthesiology 2009/ Karkouti et al. Circulation 2009/ Gauvin et al Transfusion 2008/ Scott BH et al. Ann Card Anaesth 2008/ Salim A et al. J Am Coll Surg 2008 / Ho et al. Spine 2007/ Kulier A, et al. Circulation 2007/ Murphy GJ, et al. Circulation 2007/ Bernard AC, et al J Am Coll Surg 2008/ Banbury MK et al. J Am Coll Surg 2006/ Jagoditsch et al. Dis Colon Rectum 2006/ Koch et al. Ann Thorac Surg 2006/ Koch et al. Crit Care Med 2006/ Rogers et al. Am Heart J 2006/ Surgenor SD, et al Circulation 2006/ Taylor RW et al. Crit Care Med 2006/ Leal-Noval et al. Anesthesiology 2003/ Malone DL et al. J Trauma 2003/ Chelemer et al. Ann Thorac Surg 2002/ Dunne et al. J Surg Res 2002/ Chang et al. Vox Sang 2000/ Vignali et al. Vox Sang 1996
Independent risk factor of further worsening the outcome of patients
17/09/2018

43. Transfusion Independent Risk Factor for Adverse Outcomes
Large observational studies show RBC txn is independently associated in a dose-dependent relationship with
Morbidity
LOS
Mortality
Likosky DS et al. Ann Thorac Surg 2015
Shaw et al. Transfusion 2014
Parsons J et al. Crit Care 2013
Horvath K et al. Ann Thorac Surg 2013
Linder et al. BJU Int 2013
Al-Refaie et al Surgery 2012
Ferraris V et al. Arch Surg 2012
Paone G et al. J Thorac Cardiovasc Surg 2012
Bhaskar B et al. Ann Thorac Surg 2012
Stone GW et al. Am Heart J 2012
Xenos et al. Thromb Res 2012
Ferraris et al. Ann Thorac Surg 2011
Glance L et al. Anesthesiol 2011
Ranucci M et al. J Thorac Cardiovas Surg 2011
Haijar LA et al. JAMA 2010
Beattie et al. Anesthesiology 2009
Bernard et al. J Am Coll Surg 2009
Bursi et al. Eur J Vasc Endovasc Surg 2009
Chaiwat O et al. Anesthesiology 2009
Karkouti et al. Circulation 2009
Gauvin et al Transfusion 2008
Scott BH et al. Ann Card Anaesth 2008
Salim A et al. J Am Coll Surg 2008
Ho et al. Spine 2007
Kulier A, et al. Circulation 2007
Murphy GJ, et al. Circulation 2007
Bernard AC, et al J Am Coll Surg 2008
Banbury MK et al. J Am Coll Surg 2006
Jagoditsch et al. Dis Colon Rectum 2006
Koch et al. Ann Thorac Surg 2006
Koch et al. Crit Care Med 2006
Rogers et al. Am Heart J 2006
Surgenor SD, et al Circulation 2006
Taylor RW et al. Crit Care Med 2006
Leal-Noval et al. Anesthesiology 2003
Malone DL et al. J Trauma 2003
Chelemer et al. Ann Thorac Surg 2002
Dunne et al. J Surg Res 2002
Chang et al. Vox Sang 2000
Vignali et al. Vox Sang 1996
Independent
Risk Factor
for
Adverse
Outcomes
RCTs and meta-analyses thereof show that liberal transfusion strategies appear to offer no benefit but result in increased adverse patient outcomes.
Carson et al. Cochrane Review 2012
Salpeter et al. Am J Med 2014
Rohde at al. JAMA 2014
Transfusion
Courtesy of Prof. A. Shander and Prof. A. Hofmann

44. Induces or exacerbates
Triad of
Independent
Risk Factors
for
Adverse
Outcomes
Anaemia
& Iron Deficiency
Induces or exacerbates
anaemia
Triggers transfusion
Blood Loss & Bleeding
Transfusion
Restellini S, AP&T 2012
Hearnshaw SA, et al Aliment Pharmacol Ther 2010
Blair SD, et al Br J Surg 1986
Associated w/ increased rebleeding
17/09/2018
Farmer SL., Towler SC, Leahy MF, Hofmann A. Best Pract Res Clin Anaesthesiol, (1): p
Courtesy of Prof. A. Shander and Prof. A. Hofmann

45. Anaemia & Iron Deficiency Blood Loss & Bleeding Transfusion Triad of
Independent
Risk Factors
for
Adverse
Outcomes
Anaemia
& Iron Deficiency
Blood Loss & Bleeding
Transfusion
17/09/2018
Farmer SL., Towler SC, Leahy MF, Hofmann A. Best Pract Res Clin Anaesthesiol, (1): p

46. Harness & optimise physio-logical reserve of anaemia
1st Pillar
2nd Pillar
3rd Pillar
Optimise red cell mass
Minimise
blood loss & bleeding
Harness & optimise physio-logical reserve of anaemia
Anaemia
& Iron Deficiency
Blood Loss & Bleeding
Transfusion
17/09/2018
Courtesy of Prof. A. Shander and Prof. A. Hofmann

47. Benefits of PBM Programs
ransfusion T
reduction by %
ortality M
reduction up to 68% A
verage LOS
reduction by 16-33% A
eoperation R
reduction up to 43% A
eadmissions R
reduction up to 43%
reduction of composite morbidity up to 41%, and infection rate up to 80% A
omplications C A
osts C
reduction by 10-84%
17/09/2018
Farmer et al; open anesthesiology journal 2015

48. Implementing PBM and ID/IDA treatment as a standard of care
Effective intervention
Effective implementation
Effective implementation
Enabling context
Overall
significant outcomes
Of all PBM modalities ID/IDA treatment is the most effective
The overall outcome resulting from the implementation of PBM cannot be fully appreciated and explained simply by summing the effects of the single strategies and techniques used, since these can only produce the expected optimal outcome if used in combination.

49. Focus on Patient Blood Management
‘Surgical’ PBM
Pre-surgical treatment
Post-surgical
Treatment
Intra-operative traetment
‘Medical’ PBM
17/09/2018

50. Focus on Patient Blood Management in patients undergoing surgery
‘Surgical’ PBM
Pre-surgical treatment
Post-surgical
Treatment
Intra-operative traetment
‘Medical’ PBM
17/09/2018

51. Focus on Patient Blood Management in patients undergoing surgery
‘Surgical’ PBM
Pre-operative treatment
Post-operative
treatment
Intra-operative treatment
‘Medical’ PBM
17/09/2018

52. ID/IDA is easy to diagnose, easy to treat, still easy to ignore Within Patient Blood Management ID/IDA treatment is key!
The timely application of evidence-based medical and surgical concepts designed to maintain haemoglobin concentration, optimize haemostasis and minimize blood loss in an effort to improve patient outcome
Optimize red cell mass
Minimize blood loss & bleeding
Harness & optimize physiological reserve/ tolerance of anaemia
In 2010 WHO encouraged all member states to implement PBM and identified its 3 key components:
Perioperative anaemia is one of the main risk factors for worse outcome, increased use of RBCs and increased costs in major surgical procedures and
is one of the few, that can easily be modified
Managing perioperative anaemia is one of the key elements of PBM and the opportunity for Vifor Pharma
17/09/2018

53. aneamic surgical patients
Up to 28 Millions
aneamic surgical patients
17/09/2018

54. (surgical) Patient Blood Management
Quantitative Market Analysis – concept and current issues
Total global Surgeries
Major elective surgery EU & selected partner markets
Subtypes of major elective surgery with risk of blood loss & data/ evidence availability
Currently different definitions across involved markets
Tendency of overestimating
Business opportunity cannot be concluded from ABT usage reduction (ATK approach)
17/09/2018

55. International/National policies
Patient Blood Management Program Strengthen the rationale/strategy for PBM and enable access
International Authorities
National Authorities
Hospitals
Customers
Health Economical benefit of Patient Blood Management*
Medical benefit of Patient Blood Management*
The Safety Benefit of Patient Blood Management*
Health Policy Implementation/ Payer engagement
Deliver PBM implementation «Blueprints» and integration approaches
Global
Local
PBM Strategy
Build the Rationale
Turn into
value
The PBM strategy aims to:
Identify and spell out key benefits of PBM for patients, HCPs, payers and policymakers
Demonstrate how leveraging PBM can deliver value
Identify relevant PBM policies to facilitate adoption of PBM in clinical practice
Design the most optimal ‘template’ for PBM that would maximise value for all the stakeholders and can be easily implemented locally
International/National policies
Local protocols
* focus: Anaemia Management
17/09/2018

56. Patient Blood Management
Patient Blood Management Opportunity for all involved stakeholders – a “win-win-win”
Patient Blood Management
Improving customer relations
Increasing Value
Improving Patient Safety
Improving Patient Outcomes
Reducing costs
Enhancing quality of care
↓ LoS
↓ Morbidity & mortality
↓ re-admissions
↓ more expensive procedures
↑ use of Vifor portfolio
National Blood Authorities/Blood Banks
17/09/2018

57. Different Market Archetypes to analyse success factors and build an integrated strategic framework to explore the PBM opportunity
EU Top 5
Define the “ideal” patient journey
Map critical clinical & non-clinical stakeholders
Map fund flow along the patient journey
Critical Success Factors & Building blocks Implementation Models
Analysis of internal capacities & requirements
Resource situation

58. Patient Blood Management Program Continuous sharing best practice
Interaction with governmental bodies,
blood banks, insurances,
maintenance of global expert network
PBM policies/protocols including ID/IDA correction
in the peri-operative setting
Support of local hospital protocols,
local publications & guidelines
17/09/2018

59. The global Strategy is built in parallel to the local versions based on the (s) PBM patient journey
Oct
Nov
Dec
Jan
Feb
Mar 24 31 7 14 21 28 5 12 19 26 2 9 16 23 30 6 13 20 27 CT
PBMT CT
PBMCT CT
Final Strategy & Tactics WS
Final Strategy & Tactics WS
Sign-off Meeting
Alignment with Marketing Leads** 1 2
Creation of the patient journey for Global & markets in scope
Development of draft PBM strategies/tactics for Global & markets in scope and critical success factors for PBM launch 5 6 3
Onboarding of the other affiliates***
Finalization of PBM strategy/tactics & recommendations
Creation of the PMR guide 4
External validation through primary market research for markets in scope + Italy
Policy Scan and evaluation in key countries
Today
*Workshop on draft PBM strategy/tactics, PBM building blocs & PMR
Core team: Jörg, Anna, Wolfgang
Extended team: PBMCT & Ajay Mann (UK), Alexandra Rüger (Ger), Albert Garcia (SP) and Isabelle Phitois (FR)
**1-hour TC with Marketing Lead of each market in scope + CH/AT
***Workshops/TCs with Italy & AsiaPac (South Korea, Australia (tbc))

60. Patient Blood Management Program The PBM Program Core team
Market Access
Jörg Storre (Program Lead)
Medical
Anna Mezzacasa
Marketing
Wolfgang Gessele
Market/ regional GBO representatives
YOU
Other functions (upon request/ needs)
MA/JV/ Regulatory/Legal
17/09/2018