This month, Tomas Ganz, MD, PhD, discusses the treatment of iron deficiency during pregnancy in a patient with hereditary hemochromatosis.
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I am caring for a young patient with hereditary hemochromatosis who is 36 weeks pregnant and has a ferritin level of 15μg/L. Despite the genetic diagnosis, I am tempted to order intravenous (IV) iron because of concerns about effects of iron deficiency on the fetus. How would you recommend I proceed?
The measurement of serum ferritin detects a form of ferritin secreted into blood plasma mainly by macrophages and hepatocytes, in proportion to body iron stores. Low serum ferritin is always diagnostic of depleted iron stores (with the esoteric exception of two reported cases of genetic L-ferritin deficiency). However, normal and even high serum ferritin does not rule out iron deficiency because relatively common conditions (e.g., systemic inflammation or acute liver injury) can increase serum ferritin even in the presence of underlying iron deficiency.
Defining iron deficiency by an exact ferritin cutoff based on reference cohorts of healthy pregnant women (e.g., a serum ferritin level less than 12 ng/mL) would miss many women whose ferritin is slightly above this cutoff but who do not have any iron stores. Therefore, this patient (and other women with ferritin levels <30 ng/mL) should be supplemented with iron.1
If she is not anemic (in this case anemia would be defined as Hb <10.5 g/dL, as Hb norms are adjusted for pregnancy stage), then oral iron such as ferrous sulfate 325 mg, once every other day, should be sufficient to begin to replete her iron stores, although oral iron supplementation is often tolerated poorly by pregnant women.2 If she is anemic (Hb <10.5 g/dL), then her anemia is very likely caused in part by iron deficiency and IV iron is a reasonable option. A total dose of 1,000 mg should correct her deficit and leave her with repleted iron stores after a normal delivery.3 Surprisingly, the effect of mild maternal iron deficiency on the fetus or the developmental benefits of its correction by iron supplementation are still not firmly established.4
Hereditary hemochromatosis is not of immediate concern when the patient is iron deficient. The most common form of hereditary hemochromatosis in the U.S. by far is homozygous or compound heterozygous mutations in the hemochromatosis gene HFE.5 In this condition, the severity of iron overload and its clinical significance is highly variable, but it is rare for iron overload to develop in women of reproductive age who are generally protected by menstrual blood loss, iron loss associated with pregnancies, and likely by other factors. However, once her iron deficiency is corrected, iron supplements should be stopped, and her complete blood count, ferritin and serum iron levels, and total iron-binding capacity should be rechecked in a few months to verify that she is no longer iron deficient and that the anemia was corrected by iron treatment. She should also be warned against excessive alcohol consumption, which may increase iron accumulation and the risk of iron-induced liver injury, but this is a long-term concern unrelated to her current condition. The same applies in the unlikely case that she has a severe form of hereditary hemochromatosis not caused by HFE mutations, , but her future management would have to be more active, including referral for a consultation and genetic workup by a specialized expert.
- Munoz M, Pena-Rosas JP, Robinson S, et al. Patient blood management in obstetrics: management of anaemia and haematinic deficiencies in pregnancy and in the postpartum period: NATA consensus statement. Transfus Med. 2018;28:22-39.
- Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020;105:1232-1239.
- Auerbach M, Georgieff MK. Guidelines for iron deficiency in pregnancy: hope abounds: Commentary to accompany: UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188:814-816.
- Cerami C. Iron nutriture of the fetus, neonate, infant, and child. Ann Nutr Metab. 2017;71(Suppl 3):8-14.
- Kowdley KV, Brown KE, Ahn J, Sundaram V. ACG Clinical Guideline: Hereditary Hemochromatosis. Am J Gastroenterol. 2019;114:1202-1218.
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NEXT MONTH'S CLINICAL DILEMMA
I have always given 6 months of anticoagulation for provoked deep vein thrombosis (DVT) in the thigh and 3 months of anticoagulation for provoked or unprovoked DVT in the calf. Over the last several years, I’ve noticed a trend toward giving 3 months of anticoagulation for any provoked DVT. In what situation would you give 6 months of anticoagulation for provoked thromboembolism? I would certainly give 6 months of anticoagulation for an extensive pulmonary embolism, but I’m uncomfortable giving only 3 months of anticoagulation for a DVT in the thigh.
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