Guideline 7.1 – 7.3 – Malignancy, Haematological Disease & Pregnancy

Guideline 7.1 – Malignancy:

We suggest treating symptomatic anaemia in people with CKD and cancer in those with a Hb <100 g/L. (2B)

Rationale

• Iron replacement may be used to improve haemoglobin response, and reduce RBC transfusions, for patients receiving ESA with or without iron deficiency. If patients are receiving cardiotoxic chemotherapy, iron must NOT be administered on the same day.
• ESAs may be offered to patients, on active treatment for cancer (chemotherapy), whose cancer treatment is not curative.
• If a person has an active cancer, NOT having chemotherapy treatment, DO NOT give ESA’s.
• If a person had a previous cancer which is deemed cured, then there are no concerns for giving ESA’s.

Guideline 7.2 – Haematological Disease:

We suggest ESA therapy be considered in people with myelodysplastic syndrome (MDS), myeloma and others with CKD and haematological disease. We make no recommendation on HIF-PHI therapy. (not graded)

Rationale

ESA should be considered in people with MDS with low risk MDS and symptomatic anaemia and Hb <100g/L. If a person with MDS does not respond to ESA therapy within 8-12 weeks then Haematologists should consider commencing G-CSF.

Guideline 7.3 – Pregnancy:

We recommend that pregnant and post-partum women with CKD are given parenteral iron, if indicated, from the second trimester onwards and if the benefit is judged to outweigh the potential risk for both the mother and the foetus according to SmPC guidance. (1C)

Guideline 7.3.1

We recommend that ESA therapy during pregnancy may be continued unless there is a major contra-indication (e.g., hypertension or thrombosis risks). (2C)

Rationale

During pregnancy, plasma volumes become higher than the increase in red blood cell mass, which leads to lower observed haemoglobin levels. The lower reference limit for haemoglobin concentrations in pregnancy is 110 g/L in the first trimester, 105 g/L in the second trimester and 100 g/L in the post-partum period (1, 2), with values <85 g/L associated with an estimated 62% increase in the risk of low birth weight (<2,500 g) and a 72% increase in the risk of preterm delivery before 37 weeks, across ethnic groups (3). There are no data to guide the optimum target haemoglobin for women with CKD in pregnancy (4).

The most common cause of anaemia in pregnancy is iron deficiency, which is estimated to affect greater than 40% of pregnancies (5). Iron deficiency in pregnancy can contribute to maternal mortality, increased maternal morbidity, impaired infant development and potential negative effects on pregnancy outcomes (low birth weight, placental abruption, peripartum blood loss) (2).

Pregnant women are normally offered oral iron in the first instance if Hb is below target value, however IV iron is offered if they cannot tolerate oral iron or the Hb has not responded to oral therapy (2, 6). Parenteral iron is considered safe in pregnancy and breastfeeding (7-10), although there is a paucity of safety data on exposure in the first trimester. It is important to review the SmPC for each pregnant person as foetal bradycardia may occur following administration of parenteral irons. It is usually transient and a consequence of a hypersensitivity reaction in the mother. The unborn baby should be carefully monitored during intravenous administration of parenteral irons to pregnant women.

Recent reviews have commented that ESA therapy are considered safe in pregnancy, as they are large molecules which is unlikely to cross the placenta (11, 12). They are also considered safe during lactation. Often twice to three times the use dose is required during pregnancy to achieve the desired haemoglobin target.

These recommendations are consistent with Guideline 4.6.1 of the UKKA pregnancy in CKD guidelines which states that “We recommend pregnant women with CKD are given parenteral iron if indicated”.

References

1. World Health Organisation. WHO recommendations on antenatal care for a positive pregnancy experience. 2016. Available at: https://apps.who.int/iris/bitstream/handle/10665/250796/9789241549912- eng.pdf;jsessionid=F51CF06F12EAF86C6AC57079A965078A?sequence=1 (accessed May 22nd 2019)
2. Pavord S, Myers B, Robinson S et al. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2012; 156:588-600.
3. Steer P, Alam MA, Wadsworth J et al. Relation between maternal haemoglobin concentration and birth weight in different ethnic groups. BMJ. 1995; 310:489-491.
4. Wiles, K., Chappell, L., Clark, K. et al. Clinical practice guideline on pregnancy and renal disease. BMC Nephrol 20, 401 (2019).
5. de Benoist B, McLean E, Egll I et al. Worldwide prevalence of anaemia 1993-2005: WHO global database on anaemia. Worldwide prevalence of anaemia 1993-2005: WHO global database on anaemia. 2008;
6. Albaramki J, Hodson EM, Craig JC et al. Parenteral versus oral iron therapy for adults and children with chronic kidney disease. Cochrane Database Syst Rev. 2012; 1:CD007857.
7. al-Momen AK, al-Meshari A, al-Nuaim L et al. Intravenous iron sucrose complex in the treatment of iron deficiency anemia during pregnancy. Eur J Obstet Gynecol Reprod Biol. 1996; 69:121-124.
8. Al RA, Unlubilgin E, Kandemir O et al. Intravenous versus oral iron for treatment of anemia in pregnancy: a randomized trial. Obstet Gynecol. 2005; 106:1335-1340.
9. Kriplani A, Mahey R, Dash BB et al. Intravenous iron sucrose therapy for moderate to severe anaemia in pregnancy. Indian J Med Res. 2013; 138:78-82.
10. Tariq N, Ayub R, Khan WU et al. Parenteral iron therapy in the treatment of iron deficiency anemia during pregnancy: a randomized controlled trial. J Coll Physicians Surg Pak. 2015; 25:193- 197.
11. OOliverio AL, Hladunewich MA. End-stage kidney disease and dialysis in pregnancy. Adv Chronic Kidney Dis. 2020;27:477– 485. https://doi.org/10.1053/j.ackd.2020.06.001
12. Sienas L, Wong T, Collins R, Smith J. Contemporary uses of erythropoietin in pregnancy: a literature review. Obstet Gynecol Surv. 2013; 68 (8):594-602.