Anemia in pregnancy

Common symptoms are headache, fatigue, lethargy, tachycardia, tachypnea, paresthesia, pallor, glossitis and cheilitis.[6][7] Severe symptoms include congestive heart failure, placenta previa, abruptio placenta, and operative delivery.[6][8]

In the simplest of terms, anemia results from impaired production of red blood cells, increased destruction of red blood cells or blood loss. Anemia can be congenital (i.e. conditions such as sickle cell anemia and thalassemia) or acquired (i.e., conditions such as iron-deficiency anemia or anemia as a result of an infection). The causes of anemia during pregnancy can be subdivided into two main categories; physiologic and non-physiologic causes.

Physiologic Causes

Dilutional anemia: There is an increase in overall blood volume during pregnancy, and even though there is an increase in overall red blood cell mass, the increase in the other parts of the blood like plasma decrease the overall percentage of red blood cells in

circulation.[9]

Non-physiologic Causes[7]

Iron deficiency anemia: this can occur from the increased production of red blood cells, which requires a lot of iron and also from inadequate intake of iron, which increase in pregnancy.

Hemoglobinopathies: Thalassemia and sickle cell disease

Dietary deficiencies: Folate deficiency and vitamin B12 deficiency are common causes of anemia in pregnancy. Folate deficiency occurs due to diets low in leafy green vegetables, and animal sources of protein.[10] B12 deficiency tends to be more common in individuals with Crohn's disease or gastrectomies.[11]

Cell membrane disorders: Hereditary spherocytosis

Autoimmune causes: lead to the hemolysis of red blood cells (Ex: autoimmune hemolytic anemia).[12]

Hypothyroidism and chronic kidney disease[13][14]

Parasitic infestations: some examples are hookworm or Plasmodium species

Bacterial or viral infections

Iron deficiency is the most common cause of anemia in the pregnant woman. During pregnancy, the average total iron requirement is about 1200 mg per day for a 55 kg woman. This iron is used for the increase in red cell mass, placental needs and fetal growth. About 40% of women start their pregnancy with low to absent iron stores and up to 90% have iron stores insufficient to meet the increased iron requirements during pregnancy and the postpartum period.[15]

The majority of women presenting with postpartum anemia have pre-delivery iron deficiency anemia or iron deficiency anemia combined with acute blood loss during delivery.[16]

The most useful test with which to render a diagnosis of anemia is a low RBC count, however hemoglobin and hematocrit values are most commonly used in making the initial diagnosis of anemia. Testing involved in diagnosing anemia in pregnant women must be tailored to each individual patient. Suggested tests include: hemoglobin and hematocrit (ratio of red blood cells to the total blood volume), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), erythrocyte count (number of red blood cells in the blood), red cell distribution width (RDW), reticulocyte count, and a peripheral smear to assess red blood cell morphology. If iron deficiency is suspected, additional tests such as: serum iron, total iron-binding capacity (TIBC), transferrin saturation, and plasma or serum ferritin may be warranted. It is important to note that references ranges for these values are often not the same for pregnant women. Additionally, laboratory values for pregnancy often change throughout the duration of a woman's gestation. For example, the reference values for what level of hemoglobin is considered anemic varies in each trimester of pregnancy.[21][9]

- First trimester hemoglobin < 11 g/dL

- Second trimester hemoglobin < 10.5 g/dL

- Third trimester hemoglobin < 11 g/dL

- Postpartum hemoglobin < 10 g/dL

Listed below are normal ranges for important lab values in the diagnosis of anemia. Keep in mind that these ranges might change based on each patient's stage in pregnancy:[7]

- Hemoglobin: Men (13.6-16.9), women (11.9-14.8)

- Hematocrit: Men (40-50%), women (35-43%)

- MCV: 82.5 - 98

- Reticulocyte count: Men (16-130X10^3/microL or X10^9), Women (16-98/microL or X10^9)

Differential using MCV

MCV can be a great measure for differentiating between different forms of anemia. MCV measures the average size of your red blood cells. There are three cut off measurements for MCV. If the MCV is < 80fL it is considered microcytic. If the MCV is from 80 to 100 fL then it is considered a normocytic anemia. If the MCV is > 100 fL it is considered a macrocytic anemia. Some causes of anemia can be characterized by different ranges of MCV depending upon the severity disease. Here are common causes of anemia organized by MCV.[22]

MCV < 80 fL

- Iron deficiency

- Thalassemia

- Anemia of chronic disease or anemia of inflammation

MCV 80 - 100 fL

- Iron deficiency

- Infection

- Hypothyroidism

- Liver disease or alcohol use

- Drug-induced

- Hemolysis

- Vitamin B12 or folate deficiency

MCV > 100 fL

- Vitamin B12 or folate deficiency

- Drug induced

- Liver disease or alcohol use

- Hypothyroidism

- Myelodysplastic Syndromes

Anemia is a very common complication of pregnancy. A mild form of anemia can be a result of dilution of blood. There is a relatively larger increase in blood plasma compared to total red cell mass in all pregnancies, which results in dilution of the blood and causes physiologic anemia . These changes take place to ensure adequate amount of blood is supplied to the fetus and prepares body for expected blood loss at the time of delivery.[26]

More severe forms of anemia can be a due to iron deficiency, vitamin deficiency, or other causes.

For treatment of iron deficiency anemia in pregnant women, iron supplementation at doses higher than prenatal supplements is recommended. The standard doses of oral iron ranges from 40 mg to 200 mg elemental iron daily.[30] Consult with your medical provider to determine the exact dose needed for your condition, higher than needed doses of iron supplements may sometimes lead to more adverse effects.[21]

Iron supplements are easy to take, however adverse effects in some cases may include gastrointestinal side effects, nausea, diarrhea, and/or constipation. In cases when oral iron supplement is not tolerable, other options include longer intervals between each oral dose, liquid iron supplements, or intravenous iron.[21] Intravenous iron may also be used in cases of severe iron deficiency anemia during second and third trimesters of pregnancy.[31]

Anemias due to other deficiencies such as folic acid or vitamin B12 can also be treated with supplementation as well; dose may vary based on level of deficiency.[32]

Other forms of anemias, such as inherited or acquired anemias prior to pregnancy, will require continuous management during pregnancy as well.[29]

Treatment should target the underlying disease or condition affecting the patient.

• The majority of obstetric anemia cases can be treated based on their etiology if diagnosed in time. Oral iron supplementation is the gold standard for the treatment of iron deficiency anemia and intravenous iron can be used when oral iron is not effective or tolerated from the second trimester of pregnancy onwards.[33]
• Treatment of postpartum hemorrhage is multifactorial and includes medical management, surgical management along with blood product support.[34][35]

1. Pavord, S; Myers, B; Robinson, S; Allard, S; Strong, J; Oppenheimer, C (Mar 2012). "UK guidelines on the management of iron deficiency in pregnancy". Br J Haematol. 156 (5): 588–600. doi:10.1111/j.1365-2141.2011.09012.x. PMID 2251200. S2CID 12588512.
2. Markova, V; Norgaard, A; Jorgensen, KJ; Langhoff-Roos, J (2015). "Treatment for women with postpartum iron deficiency anaemia". Cochrane Database Syst. Rev. 2015 (8): CD010861. doi:10.1002/14651858.CD010861.pub2. PMC 8741208. PMID 26270434.
3. Peña-Rosas, JP; De-Regil, LM; Garcia-Casal, MN; Dowswell, T (22 July 2015). "Daily oral iron supplementation during pregnancy". The Cochrane Database of Systematic Reviews. 2015 (7): CD004736. doi:10.1002/14651858.CD004736.pub5. PMC 4233117. PMID 26198451.
4. Dahlke, JD; Mendez-Figueroa, H; Maggio, L; Hauspurg, AK; Sperling, JD; Chauhan, SP; Rouse, DJ (2015). "Prevention and management of postpartum hemorrhage: a comparison of 4 national guidelines". Am J Obstet Gynecol. 213 (1): 761–10. doi:10.1016/j.ajog.2015.02.023. PMID 25731692.
5. Shaylor, R; Weiniger, CF; Austin, N; Tzabazis, A; Shander, A; Goodnough, LT; Butwick, AJ (2017). "National and international guidelines for patient blood management in obstetrics: a qualitative review". Anesth Analg. 124 (1): 216–32. doi:10.1213/ANE.0000000000001473. PMC 5161642. PMID 27557476.
6. Tunçalp, Ő; Souza, JP; Gűlmezoglu, M (Dec 2013). "New WHO recommendations on prevention and treatment of postpartum hemorrhage". Int J Gynaecol Obstet. 123 (3): 254–6. doi:10.1016/j.ijgo.2013.06.024. PMID 24054054. S2CID 40664131.