Anaemia in pregnancy

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Translational Obstetrics Group
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Our brief: To discuss everything about anaemia
• Iron infusions in pregnancy
• Thalassemia
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Mary is a - 28 y o G6P2 at 35+6 weeks gestation - BMI 22 - fit and healthy Mary has some questions about her recent blood test - hb 99
Working up a patient with anaemia - MCV, hematocrit - Fe studies - B12, Folate - thalassemia
Working up a patient with
anaemia in pregnancy
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Effect of anaemia on pregnancy
Pregnant women with severe anaemia (Hb <70 g/L) are at an increased risk For the fetus: preterm birth fetal growth restriction. For the mother blood transfusion, infection death in the event of an antepartum/postpartum haemorrhage delayed recovery and wound healing in the postpartum period.
Definitions of anaemia in pregnancy
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Blood volume increases by approximately 45%, peaking at about 34 week’s gestation.
The maternal plasma volume increases to a greater extent (50%) than the red blood cell mass (30% in iron- replete women) resulting in a physiological haemodilution. This creates a reduction in blood viscosity which may have benefits in tissue perfusion, including the placenta.
Anaemia in pregnancy Hb <100 g/L Severe anaemia Hb < 70g/L (WHO definition)
Iron deficiency is defined as a ferritin < 30 ug/L
Hemodilution occurs as a part of pregnancy
Definitions of anaemia
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Signs Pallor and tachycardia.
There should be a low threshold for investigating women for anaemia with a full blood examination (FBE) if symptoms are persistent or severe.
Investigations
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FBE in all women at booking, 26-28 weeks and 36 weeks.
Routine Hb checks
When to order a ferritin
Women with risk factors for iron deficiency anaemia should have a ferritin performed at the booking visit. Risk factors include: past history of iron deficiency anaemia, short interpregnancy interval (< 12 months between last birth and next pregnancy), vegetarian diet, multiple pregnancy, teenage, chronic medical conditions (eg renal or vascular disease), any risk factor for poor nutrition, including social disadvantage or recent immigration from developing country
OR If they have a microcytic anaemia
Investigations to rule out other causes
of anaemia
Translational Obstetrics
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• Low MCV (< 80) • Hb electrophoresis to assess for Beta Thalassemia and • DNA studies to assess for alpha thalassemia.
Ruling out other causes of anaemia
• High MCV (>100) • Folate • Vitamin B12 -> holocotransbalamin if the levels are low < 200 • Reticulocytosis from hemolysis
• normocytic
• Pan-cytopenia
her blood test
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Mary is a - 28 y o G1P0 at 10 weeks gestation - BMI 22 - fit and healthy Mary has some questions about her recent blood test - hb 99 - low Fe at 25
Mary has been speaking to her friends and they have suggested she get an iron infusion
Management
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Iron rich foods: Red meats are the best source: beef,
kangaroo and lamb Pork, chicken, fish Wholegrain and iron-fortified breads and
cereals Legumes Green leafy vegetables Nuts and dried fruit
Increase intake of Fe rich foods
Foods that inhibit absorption of Iron include: Calcium tablets if taken at the same time as
supplement Antacids that are calcium based Drinks rick in calcium e.g milk. Avoid drinking
with iron rich foods Unprocessed bran Tea, coffee (avoid for 2 hours pre / post oral
iron supplement)
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Translational Obstetrics
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Translational Obstetrics
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Management
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Intravenous (IV) iron in pregnancy is useful where oral iron is not tolerated or a rapid replenishment of iron is required. A total of 47 studies were eligible (21 RCTs and 26 observational studies), • All IV preparations resulted in significant improvements in haematological parameters, with
a median increase of 21.8 g/L at 3–4 weeks and 30.1 g/L by delivery • There was no evidence of any associated improvements in clinical outcomes. A greater
median increase in Hb was observed with a high (25 g/L; range: 20–39.6 g/L) compared with low dose (20 g/L; range: 6.2–50.3 g/L).
• The median prevalence of adverse drug reactions for • Iron Polymaltose (Ferrum) (2.2%; range: 0–4.5%) was lower than • Ferric Carboxymaltose(Ferinject) (5.0%; range: 0–20%) and • Iron Sucrose (6.7%; range: 0–19.5%).
While IV iron in pregnancy improves haematological parameters, there is an absence of evidence for improvements in important maternal or peri- natal outcomes. No single preparation of IV iron appeared to be superior, with the current IV iron preparation of choice largely determined by cost and conveni- ence around administration.
Management
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Management
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Management
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To examine the use, safety and efficacy of intravenous iron polymaltose in pregnancy. Retrospective cohort study intravenous IPM between January 2014 and January 2016 Iron polymaltose was administered in 213 pregnancies, • 62.0% of women with iron deficiency anaemia (IDA) and the remainder • 38.0% with non-anaemic iron deficiency. Adverse drug reactions (ADRs) occurred in 24% of women and 32% required infusion cessation. Anaemia was still present at delivery among 7%, and 17% of women with mild, and moderate/severe anaemia respectively. Intravenous IPM is effective in treating IDA in pregnancy but is associated with a high prevalence of ADRs and treatment cessation.
Our Iron infusion protocol
• IV iron replacement IV iron is a second-line treatment and is reserved for patients who: – Are unable to tolerate oral iron – Have a poor response to oral iron – Severe symptomatic anaemia with Hb <90g/L – Present with iron deficiency anaemia in late gestation
(> 36 weeks with Hb < 100g/L) • If no response to oral iron with good compliance, investigate
for malabsorption and blood loss. • If patient requires more than one dose of IV iron, consider
Haematology review
Our Iron infusion protocol Recommended Dosage of iron for IV infusion
Elemental Iron: 1000mg if weight >35kg, 500mg if weight < 35kg
Maximum dose is 1000mg, once a week Advantages of IV iron replacement - Rapid delivery of iron, avoidance of gastrointestinal side-
effects
Disadvantages of IV iron replacement - Allergic reactions and anaphylaxis (uncommon, less than 1 in 1000) - A flu-like illness is common - The need for hospital admission and close observation for administration
Management
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Management
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Use oral iron replacement
Reserve IV iron for: • < 34 weeks if Hb < 70 • > 34 weeks if Hb <90
• AND the Ferritin is < 30.
If the ferritin is normal consider another cause for the anaemia.
Consider blood transfusion if there is maternal or fetal compromise
Round 2: Folate and Vitamin B12 deficiency
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arrives
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25 y o G6P2 35+6 weeks gestation nausea and vomiting throughout pregnancy Obstetrics 2012 41 LUSCS 2.6kg FTP at 2cm 2014 STOP 2015 38 weeks elective LUSCS 2.5kg 2016 STOP 2017 medical TOP This pregnancy Lucy has had hyperemesis with multiple admissions
Vitamin B12 deficiency
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She has just had her routine bloods and these show: Hb 119 MVC 105 Ferritin 35 B12 121 (156-698) Holocotransbalomin – 17 (23-100) US 32/40 EFW 85%, AC 85% AFI Dopplers NAD
Causes of folate and Vit B12 deficiency
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Causes Folate deficiency • Diets low in animal proteins, fresh leafy vegetables, and legumes • Gastrointestinal disorders that prevent absorption of dietary folates in the duodenum
(eg, bariatric surgery) • Severe malnutrition or reduced oral intake • Chronic alcohol use, which may be associated with chronic malnutrition and increased
metabolic needs • Reduced intake of green leafy vegetables if residing in a country where cereals and
grains are not routinely supplemented with folic acid • Chronic hemolytic anemia with increased red blood cell turnover • Other conditions associated with high cellular turnover such as severe eczema Vit B 12 deficiency • Diet • Partial or total gastrectomies or those with Crohn disease
Management of vitamin B12 deficiency
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Vitamin B12 deficiency For individuals who consume a strict vegetarian diet or those with anatomic reasons to develop vitamin B12 deficiency (eg, Roux-en-Y or biliopancreatic bariatric surgery), the importance of supplemental oral vitamin B12 should be emphasized. Vitamin B12 absorption and thus is usually treated with parenteral vitamin B12, which is typically administered by intramuscular or deep subcutaneous injection at an initial dose of 1000 mcg (1 mg) once per week for four weeks then once per month.
Folic acid deficiency Folic acid supplementation is routinely recommended to prevent neural tube defects in pregnancy and these doses should prevent folate deficiency anaemia. High dose folate 5mg is used in cases of malabsorption
Take home message
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Investigate patients with megaloblastic anaemia or patients at risk of folate or Vitamin B12 deficiency
Supplement patients with Folate or Vitamin B12 deficiency orally or parentally if required
Megaloblastic anaemia is caused by folate or Vitamin B12 deficiency
Thalassemia in pregnancy
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presents
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Jasmine is a 25 y o G2P1 at 16 weeks gestation
Past history - obstetric 2014 35 week NVD 1810 g Family history - Thalassemia but not investigated Bloods at booking show: FBE Hb 105 MCV 65 ferritin 60
Types of thalassemia
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Alpha thalassemia Alpha thalassemia is highly prevalent in Southern China, Malaysia, and Thailand. Mild forms are also commonly encountered in individuals of African origin.
Beta thalassemia Beta thalassemia is highly prevalent in Africa. The estimated rate of heterozygosity in the population is approximately 13 percent in Africa, 4 percent in Asia, and 2 percent in the United States.
Types of thalassemia
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Beta Thalassemia One gene deletion – carrier Intermedia Two gene deletion – Major – Cooleys anaemia
Alpha thalassemia Carrier (one gene) asymptomatic a- thal minor (two gene) mild anaemia HbH disease (Bart’s disease three gene) hemolytic anaemia and splenomegaly Hydrops fetalis (four gene) incompatible with life.
Investigations
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Initially FBE Hb MCV <80fL MCH <27 pg Ferritin Beta-thalassemia Hb electrophoresis a-thalassemia DNA studies
Screening for sickle cell trait – Hb S determined with Hb electrophoresis
If these are positive then consider partner screening
Patients results
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Jasmine Hb electrophoresis – normal DNA studies Double gene deletion - - / a a Jamine’s husband Mohammad FBE Hb of 110 MCV of 70 DNA studies show – a / a a
Therefore their fetus is at risk of HbH disease
Fetal hemoglobinopathy typically has no adverse effects on the fetus, mother, or course of pregnancy. One exception is homozygous alpha thalassemia with the loss of all four alpha globin chains, which usually results in hydrops fetalis and death during the late second through mid-third trimester of pregnancy. Fetal hydrops can be associated with maternal mirror syndrome, which can be life- threatening for the mother
Thalassemia on the pregnancy
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Translational Obstetrics
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The loss of a single alpha-chain gene (a-/aa) causes alpha thalassemia minima (also called silent carrier). This is a benign carrier state; affected individuals are not anemic, their RBCs are not microcytic (although mild hypochromia may be noted on the blood smear), and their hemoglobin analysis is normal. The loss of two alpha-chain genes causes alpha thalassemia minor: aa/-- OR a-/a- This is a clinically mild condition characterized by mild anemia, hypochromia, and microcytosis without other clinically obvious manifestations. These conditions may remain undiagnosed, or they may be detected incidentally on a routine complete blood count during evaluation of an unrelated condition or in the setting of preconception testing and counseling.
HbH disease
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The loss of three alpha-chain genes leads to hemoglobin H (HbH) disease. The genotype can be "deletional" (ie, --/a-) The clinical severity in HbH disease is variable. Affected individuals are usually symptomatic at birth and have a thalassemia intermedia phenotype (ie, they are typically transfusion- independent) but can deteriorate into transfusion dependence. These individuals typically have mild anemia (typical hemoglobin range, approximately 9 to 11 g/dL; typical mean corpuscular volume [MCV], 62 to 77 fL and neonatal jaundice. However, there is marked clinical variability, ranging from severe anemia with fetal hydrops to an asymptomatic state.
Hydrops fetalis
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Hydrops fetalis and hemoglobin Barts — The loss of all four alpha globin genes (--/--) leads to severe anemia during fetal development with hydrops fetalis; typically this is incompatible with live birth. The only hemoglobin produced is hemoglobin Barts (Hb Barts; ie, tetramers of gamma globin). Individuals with this condition cannot produce any normal fetal hemoglobin (HbF; the major hemoglobin produced after the first six to eight weeks of gestation) or adult hemoglobin (HbA; ie, they have no HbF, HbA, or HbA2). Hb Barts cannot deliver oxygen to the tissues because its affinity for oxygen is too high (at least 10 times greater than HbA). The hydropic state in the fetus reflects the existence of massive total body edema due to high-output heart failure. Fetal death usually occurs during the late-second through mid- third trimester of pregnancy or within a few hours of birth.
Beta thalassemia major
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Beta thalassemia major have profound and lifelong transfusion-dependent anemia. Symptoms typically begin to manifest during late infancy (approximate age, 6 to 12 months); newborns are not symptomatic because their major hemoglobin is fetal hemoglobin (HbF), which uses gamma chains instead of beta chains. Presentations can be remarkably heterogeneous depending on other mitigating factors and the aggressiveness of therapy. If left untreated resents dramatically with pallor, jaundice and dark urine from hemolysis, irritability from anemia, and abdominal swelling from hepatosplenomegaly. This is followed by symptoms related to severe anemia, including high-output heart failure, failure to thrive, and infection, and expanding sites of extramedullary hematopoiesis, including skeletal abnormalities of the face and long bones, hepatosplenomegaly, and kidney enlargement. Late symptoms are mostly related to complications of iron overload, which can affect the heart, liver, endocrine organs, and others.
Beta thalassemia intermedia
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Beta thalassemia intermedia has the most heterogenous of clinical presentations. It encompasses a range of individuals, from those with chronic hemolytic anemia who are not transfusion-dependent during early childhood but subsequently become transfusion- dependent, to those with mild to moderate anemia who rarely or never require transfusions. Many of these individuals develop transfusion dependence later in life (eg, third to fourth decade) and/or require transfusions during periods of erythroid stress (eg, infections, pregnancy). Likewise, some of these individuals may develop findings associated with extramedullary hematopoiesis and some may not. Most individuals with thalassemia intermedia phenotypes develop some degree of iron overload, due both to transfusions and increased iron absorption related to ineffective erythropoiesis. However, the age at which this occurs is highly variable.
Management
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Genetic counsellor and hematology review offered amniocentesis Invasive testing – DNA-based testing for hemoglobins S and C and alpha and
beta thalassemia can be performed during the first trimester of pregnancy on villi obtained by chorionic villus sampling (typically performed at 10 to 12 weeks of gestation), or on cultured cells in amniotic fluid cells obtained by amniocentesis (typically performed after 15 weeks of gestation).
Noninvasive testing – Methods for noninvasive prenatal diagnosis of
hemoglobinopathy are being developed, but remain investigational Prior to implantation — Some couples may prefer preimplantation genetic
diagnosis because at-risk embryos can be identified before embryo transfer, thereby avoiding the need to consider termination of an affected pregnancy.
Take home message
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Perform a FBE at booking and if MVC < 80 or low MCH and ferritin
normal, consider thalassemia screening
Paternal screening with FBE then detailed study if abnormal
Consider invasive testing of the fetus
Translational Obstetrics
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