- Anemia in Pregnancy
- Hypertensive Disorders in Pregnancy
- Breech
- Pregnancy after Previous Cesarean Section
- Multiple Pregnancy
- Preterm Labor
- Post-term Pregnancy
- Intrauterine Growth Restriction
- Recurrent Pregnancy Loss
- Diabetes in Pregnancy
- Rh Isoimmunization
- Pregnancy with Heart Disease
- Antepartum Hemorrhage
- Pregnancy with Pyrexia
- Newer Viral Infections in Pregnancy
- HIV in Pregnancy
- TORCH Infections in Pregnancy
- Thyroid Disorders in Pregnancy
Anemia is the most common medical disorder encountered during pregnancy. 40–90% of pregnant women in India are suffering from anemia. As per NFHS-4 (2015–2016)1 incidence in pregnant women on an average is 50.4%.
Anemia is defined as decrease in the oxygen carrying capacity of the blood due to decrease in amount of RBCs or hemoglobin (Hb) or both. In adult female <12 g Hb% in peripheral blood is called anemia.
Causes of Anemia during Pregnancy
- Physiological
- Nutritional: Iron deficiency folate and/or vitamin B12 deficiency dimorphic
- Hemorrhagic: Acute or chronic
- Hemoglobinopathies
- Hemolytic: Congenital or acquired
- Aplastic anemia.
Physiological
Due to physiological hemodilution during pregnancy fall in Hb occurs. There is 2.5–3 times increase in plasma volume as compared to RBC mass. Maximum increase occurs in 2nd trimester. Blood volume changes during pregnancy are shown in Figure 1.1.
Due to this, anemia in pregnancy is considered as per center for disease control (CDC) modified WHO definition as follows:
Hb%: | <11.0 g% in 1st and 3rd trimester |
<10.5 g% in 2nd trimester |
Degrees of anemia
ICMR | WHO | |
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Mild | 10–10.9 g% | 9–10.9 g% |
Moderate | 7–9.9 g% | 7–8.9 g% |
Severe | 4–6.9 g% | <7 g% |
Very serve | <4 g% | — |
Postpartum | — | <10 g% |
Nutritional Anemia
In India 90% of anemia in pregnancy are of nutritional origin. Iron deficiency is by far the most common cause of nutritional anemia.
Iron Deficiency Anemia
Iron is the essential element of heme pigment of the Hb. Deficiency of iron during pregnancy in our country is due to following reasons:
- Low iron intake: As iron cannot be produced in the body, it is essential to eat food that contains iron. Dietary sources rich in iron are mentioned in Table 1.1. Cooking in iron utensils is helpful.
- Increased nutrient demand: There is increased demand of iron during pregnancy. Each pregnancy needs approximately 1 g (1,000 mg) of extra iron as shown in Table 1.2.Most of this is required in second half of pregnancy. Although iron absorption increases during pregnancy (20–30% from normal 10%) the average vegetarian diet does not contain enough iron (10 mg average) to fulfil this demand.So, if woman has depleted iron stores, she requires 6–7 mg iron/day during second half of pregnancy, while woman with good iron stores 3–4 mg/day is sufficient. Thus iron supplement during pregnancy is must for an Indian mother.
Table 1.2 Iron requirement during pregnancy. Expansion of RBC400–500 mgFetus (80 mg/kg)200–250 mgPlacenta and cord80–100 mgBasal losses220–250 mgTotal900–1,100 mgAverage 1,000 mg (1 g)Saving of iron due to amenorrhea during pregnancy (25 × 8 = 200 mg) compensates for blood loss at delivery (150–200 mg). - Poor absorption and utilization: The Indian diet which is predominantly vegetarian contains many substances which inhibit iron absorption. The factors influencing iron absorption are mentioned in Table 1.3.Also the bioavailability of nonheme iron (vegetarian diet) is poor and is slowly absorbed as compared to heme iron (5–10% vs 35–40%).
- Poor reserve: Normal iron store in adult female is 300–500 mg. An average Indian woman enters her first pregnancy with inadequate or poor iron stores. This is due to inadequate nutrition during adolescent period because of gender bias, poverty, and less education.In parous women repeated pregnancies at short intervals (<2 years) and prolonged lactation (without iron supplement) also leads to depletion of iron stores.
- Increased loss: The increased loss is due to high incidence of malaria and hookworm infestation. In rural areas hookworm infestation is common. This leads to average blood loss from 0.03 (Necator americans) to 0.2 mL (Ankylostoma duodenale) per parasite/day. In heavy infestation daily loss of iron can be up to 5 mg. Excessive menstrual loss (before pregnancy) and sweating are also responsible.
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IRON METABOLISM
Total body iron depends upon age, sex (more in male) and body weight of the person. In an adult female it is 2.0–2.5 g (35–40 mg/kg). It is distributed in the body as shown in Table 1.4.
Absorption
- Exact mechanism of absorption is still not known.
- Iron is mainly absorbed from duodenum.
- Nonheme iron (vegetarian diet) is mostly in ferric (Fe+++) form. It has to be reduced to ferrous (Fe++) form for absorption.
- Due to acidic pH of the stomach and other reducing agents Fe+++ is reduced to Fe++.
- A transporter protein called divalent metal transporter 1 (DMT 1) of enterocytes transports Fe++ iron from duodenal lumen to inside the enterocyte. With the enzyme peroxidase it is converted to ferric (Fe+++) iron.
- Ferric iron can have one of the two fates: (1) Iron combines with apoferritin to form ferritin which is deposited in the intestinal cells and eventually excreted on their desquamation. (2) Iron which is not combined with apoferritin is absorbed and circulated in the plasma as ferric form combined with transferrin.
- Heme iron is in Fe++ form so its absorption is 2–3 times more than nonheme iron. Heme iron is present in hemoglobin and myoglobin (i.e., nonveg diet).
- Absorption of heme iron is not decreased by other foods simultaneously ingested.
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Transport
- Fe+++ is taken up by transferrin (siderophilin), an iron-binding protein present in the blood for transportation to various parts of the body.
- Transferrin receptors present in the various cells of the body including RBCs (erythropoiesis) recognize transferrin leading to the entry of complex into the cell. Iron is released intracellularly. While transferrin is released back into the circulation to carry fresh load of iron.
- Iron from the breakdown of senescent RBCs in the reticuloendothelial system (RES) is also transported by transferrin for recycling in erythropoiesis.
Storage
- Some iron is stored in the RE cells in the liver, spleen and bone marrow as ferritin (major portion) and hemosiderin.Fe+++ + Apoferritin = FerritinAggregate of ferritin = Hemosiderin
- Ferritin can accommodate up to 4,500 of iron atoms. Ferritin is water-soluble while hemosiderin is not. Stores are mobilized to provide iron as and when need arises. In iron deficiency first the stores are depleted.
Excretion
- About 0.8–1.0 mg of lost iron is daily through exfoliated gastrointestinal (GI) mucosal cells, skin and in stool, urine, and sweating. In female approximately 1.0 mg/day should be added for menstrual loss during reproductive age group.Iron cycle is mentioned in Figure 1.2. As there is no physiological mechanism for 6iron excretion, which is almost constant; iron content of the body is regulated by absorption alone. The amount of iron absorbed from the diet depends upon iron stores and requirement for erythropoiesis. Factors affecting iron absorption are mentioned in Table 1.5 (food factors affecting the absorption of iron are already mentioned in Table 1.3).
- Drugs, such as Alphadopa, Levodopa, Ciprofloxacin, and Cimetidine interfere with iron absorption.
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Iron deficiency occurs in three stages
First stage: | Depleted iron stores. |
Second stage: | Decrease in serum iron and increase in total iron-binding capacity (TIBC). There is deficient erythropoiesis. |
Third stage: | Iron deficiency anemia. |
Thus decrease in Hb represents very late stage of iron deficiency.
Erythropoiesis
RBCs are formed in the red bone marrow situated in the ends of long bones, from nucleated cells known as stem cells or hemocytoblasts.
Stem cells → Proerythroblast → Basophilic erythroblast (early normoblast) → Polychromatophilic erythroblast (intermediate normoblast) → Acidophilic erythroblast (late normoblast) → Reticulocyte → Erythrocyte (RBC)
From proerythroblast to reticulocyte it takes 7 days. From reticulocyte to mature RBC it takes 2 days. Erythropoiesis is stimulated by the hormone erythropoietin secreted from the kidney. Erythropoiesis is stimulated if there is tissue anoxia or if the red cell count goes down.
Clinical Features
Symptoms
- Fatigue, weakness, lassitude, impaired work capacity
- Dizziness, giddiness, headache, insomnia
- Dyspnea on exertion, palpitation
- Anorexia, dyspepsia
- Edema of ankles.
Signs
- Pallor of skin and mucous membrane. In severe anemia there is even loss of color in the palmar creases.
- There may be glossitis, stomatitis and dysphagia.
- Koilonychia (changes in nails: Initially brittleness and dryness, later there is flattening and finally concavity, i.e., spoon-shaped nails).
- Tachycardia.
Effects of Anemia in Pregnancy
Mother
- Increased susceptibility to infection.
- Cardiac failure at 30–34 weeks of pregnancy if severe anemia.
- Pre-eclampsia may be related to malnutrition.
- Preterm labor (3 times greater risk).
Labor
- Uterine inertia.
- Postpartum hemorrhage—even moderate blood loss can lead to collapse.
- Cardiac failure
Puerperium
- Cardiac failure
- Puerperal sepsis
- Subinvolution
- Failing lactation
- Chronic ill health, backache.
Fetus and Neonate
- Prematurity
- Intrauterine growth restriction (IUGR) (3 times increased risk).
- Increased perinatal deaths.
- Decreased iron stores in neonate (Hb level in the fetus or neonate is not affected in anemic mother but soon infant can develop anemia due to deficient iron store).
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Diagnosis
Although clinical history and examination (pallor) are suggestive, following investigations are done. Investigations are carried out for:
- Diagnosis and degree of anemia: Clinical estimation can be erroneous. Hb estimation is used for diagnosis. Hb below 11.0 g% suggests pathological anemia. Value of mild, moderate and severe degrees are already mentioned before.RBC count <3.2 million and packed cell volume (PCV) <30% suggest anemia.
- Type of anemia:
- Peripheral smear (PS): To study the morphology of RBCs. It shows microcytic hypochromic picture in iron deficiency anemia. RBCs are smaller in size with central pallor. Also there is anisocytosis (variation in size) and poikilocytosis (variation in shape). PS may also help in diagnosing malarial parasites. Reticulocyte count may be slightly raised. Occasionally target cells are present.
- Hematological indices: These are mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Their values in iron deficiency anemia as compared to normal are mentioned in Table 1.6.
- Specific investigations for iron deficiency include serum iron, TIBC, percentage saturation (serum iron/TIBC), serum ferritin level (Table 1.6). In fact decreased ferritin level is the first feature of iron deficiency.8Free erythrocyte protoporphyrin (FEP) and transferrin receptor levels are not routinely carried out. They increase early in case of iron deficiency and are more sensitive than even ferritin.Bone marrow examination: This is not routinely done. It is only indicated in—(1) refractory anemia and (2) aplastic/hypoplastic anemia. In iron deficiency anemia iron stores are absent. The absence of stainable iron is ‘gold standard’ for IDA.
- Cause of anemia: For diagnosing the cause, detailed history is also important, e.g., food habits, obstetric history (multipara, short intervals), gynecologic history (menorrhagia), history of malaria or worms.
- Urine examination: Routine and microscopy (culture studies if indicated) are done for diagnosing urinary tract infection (UTI), asymptomatic bacteriuria, hematuria, etc.
- Stool examination: Ova (eggs), cysts and for occult blood. Eggs of hookworm are segmented (4 blastomeres) and float in saturated solutions of common salt.
- Serum proteins: Hypoproteinemia.Special tests may be carried out in megaloblastic and other rare anemias.Serum folate, RBC folate—megaloblastic anemiaSerum vitamin B12Serum bilirubin—hemolytic anemia.Coomb's tests—autoimmune hemolytic anemiaSickle test—sickle cell syndromesHb electrophoresis—hemoglobinopathies.
Naked eye single tube red cell osmotic fragility (NESTROF) test2—beta thalassemia trait. Glucose-6-phosphate dehydrogenase (G6PD) screening,
Red cell osmotic fragility test—hereditary spherocytosis.
Causes of microcytic anemia:
- Iron deficiency anemia
- Thalassemia
- Anemia of chronic disease
- Sideroblastic anemia
- Lead poisoning
- Anemia associated with copper deficiency
- Alcohol use.
Management
General preventive measures are:
- Screening of adolescent girls in school and giving iron supplements.
- Education and motivation for taking diet rich in iron (Table 1.1).
- Change in food habits, i.e., avoiding tea or coffee for at least 2 hours after meals.
- Prevention of hookworm and malaria. For hookworm, Albendazole 400 mg stat or Mebendazole 100 mg BID for 3 days is recommended. For malarial prophylaxis weekly 2 tablets of Chloroquine (300 mg base) are given from 2nd trimester onwards in endemic areas.
- Keeping adequate interval between pregnancies (>2 years minimum) and avoiding prolonged lactation without iron supplement.
- Fortification of food by iron, i.e., 30–36 mg iron should be added per kg of wheat flour.
- Fortification of common salt by iron.
- Cooking in iron utensils is helpful.
Govt of India (Ministry of Health and Family Welfare) has recommended 100 mg of elemental iron + 0.5 mg FA/day for 100 days to every pregnant woman in our country as prophylaxis from second trimester onwards and postpartum for 6 months. Dose is to be doubled if there is mild anemia.
Treatment
Apart from treatment of the cause, iron therapy for correction of anemia as well as to replenish the iron store is essential.
Iron Therapy
- Oral iron therapy: It is indicated in all mild and moderate iron deficiency cases. It is cheap, safe and effective in most of the cases. 100–200 mg elemental iron per day 9is recommended. Different common iron salts with their elemental iron content is mentioned in Table 1.7.
- Ferrous salts are 3 times readily absorbed than ferric salts.
- Ferrous sulfate is the cheapest and well absorbed form of iron.
- Ferrous gluconate is well tolerated but it has low iron content (36 mg in 320 mg tablet).
- Ferrous fumarate is the most commonly used salt in commercial preparations.
- Ferrous ascorbate is a synthetic molecule of ascorbic acid, iron and as ascorbate makes stable chelate with iron there is no dissociation in GI tract, so there is no action of food inhibitors. Tablets containing 100 mg elemental iron is available for use.
- Carbonyl iron: Newer market preparation contain this. Carbonyl refers to manufacturing process where iron is obtained by thermal decomposition of iron pentacarbonyl which when heated to above its boiling point decomposes to give iron and carbon monoxide. Iron thus obtained has high purity (>98%), very fine spherical size (<5 μ) and uniform particle size. It is easily absorbed and less toxic than ionized forms of iron, such as iron sulfate. It has a high safety range.
Table 1.7 Oral iron preparations. SaltTabletElemental ironFerrous sulfate200 mg60 mg (30%)Ferrous fumarate200 mg66 mg (33%)Ferrous gluconate320 mg36 mg (12%)Ferrous succinate100 mg35 mg (35%)-Ferric ammoniumcitrate125 mg25 mg (17–22%)Ferrous ascorbate—100 mgIPC—100 mgCarbonyl iron—90 mgSodium feredetate—231 mgFerric pyrophosphate—30 mg - Sodium feredetate: It contains ferric sodium EDTA. It contains iron in a unionized form. It is not astringent and does not discolor teeth. Its absorption is less affected by food inhibitors, such as phytates.Ferric pyrophosphate: It is relatively newer iron preparation with advance microsomal technology. It leads to lower GI side effects than conventional oral iron preparation.Faster rise of Hb is claimed by manufacturer.
- Micronization of iron and encapsulation with liposomes increases bioavailability.Ferrous bisglycinate chelate: It is a chelated form of iron, where two molecules of amino acid glycine are bound to a molecule of iron. It does not cause gastric irritation and constipation. Absorption of bisglycinate is not affected by phytates in food.
- Iron polymaltose complex (IPC): It is ferric hydroxide polymaltose complex. It is nonionic and it does not stain the teeth. There is no metallic taste and no interaction with food or other drugs. Initially claimed high therapeutic results were not found in clinical practice, so it is less used now.
- Sustained-release (SR) or time release (TR) preparations have less GI side effects but lesser iron is released in the main absorptive area, i.e., duodenum and upper jejunum and so less is absorbed.
- Gastric delivery system (GDS) contains ferrous sulfate in a gel forming polymer matrix, so the tablet floats in the stomach for 5–12 hours releasing small amount of iron to the main absorptive area (i.e., duodenum). It is claimed that 3 times more iron is absorbed with less side effects.
Iron prescription:- If there is swallowing problem or intolerance use liquid preparation (less side effects but staining of teeth may be a problem).
- Iron should be taken on empty stomach with fruit juice for better absorption, i.e., 1 hour before or 2 hours after meals. Due to stomach upset it is usually taken with the meals.
- Tea, coffee avoided for 2 hours after taking iron.
- Taking vitamin C helps in absorption.
- Calcium salts (except calcium carbonate and calcium citrate) and antacids should be avoided.
Response:- Reticulocyte count increases by 7–10 days.
- Hb% rises at 10–14 days. About 1 g%/week rise in Hb occurs from 2nd week onwards.
Side effects of oral iron: Upper GI tract—nausea, gastric discomfort, loss of appetite and eructation. Staining of teeth particularly in liquid preparation.Lower GI tract—constipation, diarrhea, and flatulence.Nonresponse to oral iron: Reasons can be:- Noncompliance due to intolerance or otherwise.
- Poor absorption
- Wrong diagnosis another etiology of anemia.
- Continued loss of iron.
- Parenteral iron therapy: It is indicated when:
- Intolerance to oral iron.
- Noncompliance to oral iron.
- Poor absorption of oral iron (malabsorption syndrome, dysentery, etc.)
- No response to oral iron after 4 weeks in a confirmed case of iron deficiency anemia.
- Some cases of moderate anemia (6–8 g Hb) very late in pregnancy.
Preparations:- Iron sucrose: It is available as 20 mg/mL in 5 mL (100 mg) or 10 mL (200 mg) ampoules.
- Ferric carboxymaltose (FCM) available as 50 mg/mL in 5 mL or 10 mL vials.
Iron sucrose:- It is category B drug.
- Dose calculation is total iron = 2.4 × weight in kg × deficit of Hb in g. 500 mg should be added for pregnancy.
- It is safer, effective and well tolerated.
- Test dose is not recommended. However, some authorities prefer to give test dose.
- It can be given undiluted IV slowly 1 mL/min OR diluted 100 mg in/100 mL of normaI saline and given IV over 15 minutes.
- Maximum 200 mg per dose is given repeated up to three times a week.
- Iron sucrose is dissociated by the reticuloendothelial (RE) system into iron and sucrose. The released iron increases Hb. 75% sucrose is excreted by kidney in 24 hours.
- It is claimed that there is rapid rise of Hb than oral iron, i.e., after 1 week and also rapid buildup of iron stores.3
- It cannot be given IM due to alkaline pH (>10) as it causes muscle damage.
- It is not stable in dextrose, so it cannot be diluted in dextrose.
Ferric carboxymaltose (FCM):- It is newer parenteral iron where ferric hydroxide core is stabilized by carbohydrate shell so there is controlled release of iron leading to decreased oxidative stress.
- It was initially recommended only for postpartum use but now safety during pregnancy is established.
- Dose is calculated as per standard formula and single dose is given in not <15 minutes in 250 mL saline.
- Minor adverse reactions in the form of injection site redness, swelling or nausea, vomiting, headache may occur in few patients.
- It elevates Hb level and restores iron stores faster than oral iron or even IV iron sucrose.4
Iron sorbitol citric acid complex:- 0.5 mL (25 mg) test dose should be given.
- 100 mg/day is given daily or on alternate days (75 mg Jectofer).
- It is given deep IM by “Z” technique to prevent skin staining.
- Side effects are: (1) it is painful; (2) discoloration of skin; (3) injection abscess; (4) sarcoma is reported in rats (Imferon) but not in humans.
Iron dextran (Imferon):- It was used in past. It was given IM or IV after test dose.
- Side effects include: Thrombophlebitis at IV site, malaise, fever, arthralgia, urticaria, lymphadenopathy.
- Anaphylaxis is the real risk. Rarely deaths also have been reported. So total dose Imferon is not practiced at present.
- Iron intoxication: Wrong diagnosis of iron deficiency anemia or there is already iron overload (thalassemia).
- Advantages of IV over IM therapy are: (1) it is less painful; (2) complacency is better—complete treatment is ensured; and (3) less hospital stay.
- Oral iron should be stopped for at least 48 hours before parenteral therapy to prevent intoxication.
- Sodium ferric gluconate:
- It is given IV 10 mL (125 mg) diluted in 100 mL normal saline (available 12.5 mg/mL).
- It is mainly used for iron deficiency in hemodialysis patients.
- Side effects include nausea, vomiting, hypersensitivity reaction and hypotension.
- Erythropoietin: Recombinant human erythropoietin is mainly useful for anemia in patients with renal disease and on cancer chemotherapy. In pregnancy as such erythropoietin levels are increased. It is given 150 IU/kg subcutaneous (SC) thrice a week with iron supplements.
Blood Transfusion
It is indicated in iron deficiency anemias in following cases:
- Severe anemia (Hb <7.0 g) at any gestational age.
- Moderate anemia beyond 36 weeks and when there is failure of response to iron therapy.
Blood transfusion is also indicated in many obstetric situations:
- Severe hemorrhage—antepartum hemorrhage (APH), PPH, rupture uterus at cesarean section, severe first trimester hemorrhage.
- Thalassemia and sickling disorders in pregnancy.
As per RCOG guidelines PCV is given during pregnancy as follows:
- <34 weeks. If Hb <5 g with or without cardiac failure or hypoxia; 5–7 g in presence of impending failure.
- >34 weeks. If Hb <7 g even without cardiac failure or hypoxia.
Whole blood transfusion should not be used. Packed cells volume (PCV) transfusion is better than whole blood as patient will have less—(1) volume overload, (2) less transfusion reactions and (3) components separated from whole blood can be used for other patients. Properly grouped, typed and “X” matched PCV should be used. 1 unit increases hematocrit by 3–4% or Hb by 0.8–1.2 g% depending upon blood volume of the patient and Hb level of PCV transfused.
Steps of PCV transfusion
- Patient's sample is collected in plain and EDTA (2–3 cc each) and sent to blood bank after proper labeling with requisite form for grouping and ‘x’ matching.
- Demand is sent for supply of unit of PCV when required.
- PCV bag is released from blood bank after proper grouping and ‘x’ matching with standard form having all details.
- PCV bag supplied is doubly checked with blood bank form and patient's case paper.
- Identification at bedside is advisable.
- There is no need to warm the bag or to bring it to room temperature.
- Rate of transfusion is 15 drops/min initially for half an hour to check for any immediate adverse reaction.
- Then the rate is increased and whole unit is transfused taking 4 hours.
- Vitals are recorded before starting the blood and then after half hourly.
- Few cc of blood is left behind in the bag.
- The empty bag with necessary form is always returned to blood bank.
- Diuretic may be given at the end of transfusion to prevent overload.
Exchange transfusion
- This particularly indicated in severe anemia with congestive cardiac failure (CCF).
- PCVs are transfused (minimum 3 units) through one antecubital vein and simultaneously whole blood is withdrawn from opposite femoral vein.
- Blood withdrawn should be 200 mL more than the amount transfused, i.e., keeping negative balance.
Adverse reactions to blood transfusion
- Transfusion reactions: The most dangerous is acute hemolytic reaction due to mismatched transfusion which can be fatal. They are mentioned in Table 1.8.
- Infections: Viral: Hepatitis B, hepatitis C, human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), cytomegalovirusBacterial: Syphilis, gram-negative bacteriaParasitic: Malaria.
- Volume overload: If whole blood is transfused in chronic severe anemia and if diuretic is not used.
- Others: These include hypothermia, citrate toxicity, hyperkalemia secondary to increased potassium in stored cells, hypocalcemia (secondary to binding of calcium by citrate based anticoagulant), iron overload (in thalassemia) and disseminated intravascular coagulation (DIC)(dilution coagulopathy in massive blood transfusions) and rarely air embolism.
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As per RCOG guidelines PCV is given during pregnancy as follows:
- <34 weeks If Hb <5 g with or without cardiac failure or hypoxia.
- >34 weeks Hb <7 g even without cardiac failure or hypoxia.
Management in labor
- Mild sedation or pain relief is done.
- Oxygen is given by mask if dyspnea occurs.
- Strict asepsis is ensured.
- PCV should be kept ‘x’ matched and ready.
- In severe anemia digitalization may be required if CCF occurs.
- Second stage should not be prolonged and prophylactic forceps (preferred) or vacuum should be done.
- Active management of 3rd stage of labor should be done, as these patients may not tolerate even mild PPH (10 units IM oxytocin).
Puerperium
- Adequate rest is ensured with early ambulation.
- Prophylactic antibiotics are given.
- Fatigue, weakness, feeding problems are common.
- Iron and folic acid (FA) supplements should be continued for 6 months.
Folic Acid Deficiency Anemia
FA along with vitamin B12 is required for synthesis of thymidine in the body, which is a necessary precursor of deoxyribonucleic acid (DNA) synthesis and red blood cell (RBC) formation, so their deficiency leads to impaired growth, maturation of RBC and anemia known as megaloblastic anemia.
Pure folic acid deficiency anemia is hardly 3–4%, but it is usually associated with cases of iron deficiency anemia causing dimorphic anemia. With increased awareness and routine supplement of folic acid during pregnancy it is decreasing nowadays.
Etiology:
- Increased demand due to pregnancy and lactation, poor intake (low socioeconomical class, alcoholics) and malabsorption (tropical sprue, celiac disease) are the main causes.
- It is more common in multiple pregnancy, multigravida patients and also in chronic hemolytic states.
- Dietary rich sources of FA are dark green vegetables (the word folic acid comes from Latin word ‘folium’ means leaf), nuts, sprouts, sweet potatoes, fruits. Vegetables include spinach, broccoli, asparagus, lentil, legumes, and mushroom.Liver and kidney are rich nonveg sources.
- FA absorption or metabolism may be impaired by drugs, such as oral contraceptives, pyrimethamine, primidone, phenytoin, barbiturates and sulfa + trimethoprim.
- Prolonged cooking leads to loss of vitamins and lack of raw food in diet also leads to deficiency.
Absorption and storage: FA is mainly absorbed from the proximal jejunum. In the circulation it may be free or loosely bound to plasma protein β-globulin. The liver is the principle storage depot. It stores 6–10 mg of folic acid.
Clinical features: Anemia usually develops in late pregnancy or early puerperium. General symptoms as mentioned in iron deficiency anemia are present. In long standing cases glossitis, dry lips and roughness of skin are more evident. Intense anorexia aggravates the dietary deficiency.
Diagnosis: Apart from low Hb other hematological diagnostic parameters are mentioned in Table 1.9. Formiminoglumatic (FIGLU) acid excretion test diagnostic of FA deficiency is not useful in pregnancy because there is increased utilization of histamine by fetus as pregnancy advances.
Earliest morphological change is hypersegmentation of neutrophils.
Term megaloblastic represents bone marrow picture. Only in severe cases megaoblasts appear in peripheral blood. Megaloblastic is viewed as unbalanced growth between cytoplasm and nucleus, due to improper and defective synthesis of nucleoprotein.
For diagnosis of megaloblastic anemia at least 2 of the following features must be present in the films of buffy coat layer.
- >4% neutrophils must have >5 lobes.
- Presence of orthochromic macrocytes (diameter >12 um).
- Nucleated RBCs are found (i.e., normoblasts showing premature hemoglobinization for their stage of nuclear development).
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- Macropolycytes (giant polymorphs) present.
Effects on pregnancy: Apart from megaloblastic anemia FA deficiency was believed to cause abruptio placenta, spontaneous abortion and IUGR but it is not definitely proved. The only proved association of FA deficiency in first trimester is that it causes open neural tube defects, e.g., anencephaly, spina bifida, etc., in the fetus. Fetus otherwise is not anemic. It effectively extracts folate from maternal circulation.
Management: Prophylaxis—along with iron, folic acid 0.5 mg/day is recommended to every pregnant mother. Conventional hematinic preparation contains 0.5–1.5 mg FA along with iron and other micronutrients. For prevention of neural tube defects higher doses, i.e., 5 mg/day is given and it is started 3 months preconceptional.
Treatment:
- 1–5 mg/day orally is usually given.
- Injection FA is rarely required, i.e., in presence of GI disorders, such as sprue, or rarely for deficiency diagnosed late in pregnancy.
Vitamin B12 Deficiency Anemia
- As mentioned previously along with folic acid it is required for DNA synthesis.
- It has very little daily requirement and long storage life.
- In pregnancy its deficiency can occur in strict vegetarians. It can also occur in patients with history of gastrointestinal surgeries, inflammatory bowel disease and helminthic infestation.
- Severe deficiency is usually associated with infertility.
- Common dietary sources are meat, fish, poultry, and dairy products.
- It is absorbed in the ileum, bound to intrinsic factor. Intrinsic factor is secreted in the stomach by the parietal cells.
- Main storage site is liver.
- Addisonian pernicious anemia (lack of intrinsic factor) is rare in pregnancy due to: (1) patients are usually infertile, (2) occurs after 40 years of age, and (3) not common in India.
- Recommended dietary allowance is mentioned in Table 1.10. Hematology is same as seen in FA deficiency anemia except that plasma and RBC folate levels are normal and vitamin B12 level is <100 pg/mL (Normal: 150–950 pg/mL).
Comparison of folic acid and vitamin B12 are mentioned in Table 1.11.
Effects on pregnancy: It produces megaloblastic anemia so effects on pregnancy are those of anemia. Subacute combined degeneration of spinal cord due to vitamin B12 deficiency is almost uncommon in pregnant patient.
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Treatment:
- Oral preparations have unreliable absorption properties and are inadequate for long-term treatment.
- Injection vitamin B12 1,000 μg (1 mg) IM once a week is recommended for 6–8 weeks.
- Most of the oral hematinic preparations include FA + vitamin B12 along with iron.
Dimorphic Anemia
Combined defect of hematopoietic factors is common than isolated defect so, nutritional anemia, in upto 40% of cases are dimorphic anemia, i.e., iron + folic acid (rarely vitamin B12) deficiency.
- Dietary inadequacy and intestinal malabsorption are the common causes.
- Clinical features will depend upon the relative proportion of the deficient factors apart from degree of anemia.
- Different hematological parameters are mentioned in Table 1.12.
- Hematological features will also depend upon the relative deficiency. When one deficiency is predominating it may mask the expression of other deficiency.
- Macrocytic hypochromic picture suggest both deficiency. Low serum iron and serum ferritin as well as low serum folate/vitamin B12 levels are seen.
Hemorrhagic anemia: Hemorrhage can be acute or chronic. In pregnancy acute hemorrhage is common.
- Acute hemorrhage: Rapid and severe blood loss may be associated with:
- Abortion, ruptured ectopic or gestational trophoblastic diseases in early pregnancy.
- Antepartum hemorrhage in late pregnancy.
- Intra- and postpartum due to PPH, rupture uterus and some cases of cesarean section.
- Chronic hemorrhage: This may be due to piles, peptic ulcer, worm infestation, dysentery and drugs (not with low dose aspirin).
Hemoglobinopathies
It is a collective term used for genetic (autosomal recessive) disorders affecting the globin portion of hemoglobin molecule. Hemoglobin consists of heme (haem) + globin. Globin is made up of 2 pairs of peptide chains each attached to heme complex.
The composition of different Hb and their percentage in adult are mentioned in Table 1.13.
Hemoglobinopathies are further divided into:
- Thalassemia syndromes: Reduced or absent synthesis of structurally normal globin chains (quantitative defect).
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THALASSEMIA SYNDROMES
- Greek word Thalassic means sea. depending upon which synthesis is affected it is called oc thalassemia or β thalassemia. The incidence of thalassemia in pregnancy for all races is 1 in 300–500.
- Alpha thalassemia: High incidence is found in Far East, Malaysia, South China and also in South East Asia. The genes for OC globin chain are present on chromosome 16. It is in pair inherited from each of the parent. So normal individual genotype is OCOC/OCOC. The defect in OC thalassemia is of deletion type. The disease severity increases as the deletion of gene increases. Different types of OC thalassemia are mentioned in Table 1.14. OC 0 thalassemia is characterized by deletion of both genes from one chromosome (– –/OCOC). It is also known as Alpha thal-1. It is more seen in Asian population. OC + Thalassemia is characterized by loss of single gene from one chromosome, i.e., OC/OC – and OC –/OC –. It is also known as alpha thal-2. It is more seen in African population.
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Clinical Picture
- Silent carrier state: No clinical or hematological abnormality is evident.
- OC thalassemia minor (OC–/OC–, OCOC/– –):
- Mild microcytic, hypochromic anemia.
- Hb may be slightly decreased but usually patients tolerate pregnancy well.
- Oral iron and folic acid are given.
- Parenteral iron should be given.
- Blood transfusion may be required.
- Diagnosis is made by low MCV and MCH but serum iron serum ferritin levels are normal or raised (unlike iron deficiency anemia) and Hb A2 <3.5% on electrophoresis (unlike beta thalassemia).
- Fetus may inherit the carrier state.
- If both the parents are minor (OC 0 type) the fetus may be major (25%). Here prenatal diagnosis has a role.
- HbH disease (OC –/– –):
- HbH results due to deletion of 3 genes leading to tetramer of beta chains β4.
- These individuals have normal expectancy but chronic hemolytic anemia of moderate to severe degree exists.
- In adult, 5–30% of Hb is HbH. Though it is stable and soluble, conditions of oxidant stress causes it to precipitate and hemolysis occurs.
- Anemia worsens during pregnancy and blood transfusions are often required.
- Homozygous OC thalassemia (OC thalassemia major) (– –/– –):
- Due to deletion of all 4 genes, OC chain is not synthesized at all.
- Tetramer of gamma chains (γ4), i.e., Hb Bart's occurs.
- Hb Bart's has very increased affinity for oxygen so it does not deliver it to fetus adequately. Fetus suffers from hypoxia and develops hydrops (no immune) and dies in utero. Thus pregnant patient with OC thalassemia major is not seen.
- Patient can develop severe preeclampsia if fetus is having thalassemia major (hydrops).Beta thalassemia: It results from decreased (β+) or absent (β0) synthesis of beta chain. Beta chain synthesis in 17fetal life begins at sixth week of gestation and Hb A (α2γ2) appears at 11th week of gestation. Gene for β chain is located on chromosome 11. Unlike OC chain it is single gene from each parent and not pairs so genotype of normal individual is β/β. Also unlike OC thalassemia the defect is not by deletions of gene but it is by point mutations of the gene.Heterozygous β thalassemia—β thalassemia minor. Homozygous β thalassemia—β thalassemia major. Other names for β thalassemia major are—Cooley's anemia, Mediterranean anemia (Thomas Cooley from Detroit first described this condition).High incidence is found in Mediterranean area, the Middle East, Indian subcontinent and the Far East. In India it is more found in Kutch people (Gujarat) and in Sindhi, Lohana community.
- β Thalassemia major: In intrauterine life main Hb is Hb F (α2γ2) so fetus is not much affected (unlike homozygous alpha thalassemia). But after birth, the normal replacement of Hb F by Hb A2 does not occur due to absence of β chain. This leads to increased production of OC chains. Tetramer of OC chains (OC4) occurs which is insoluble and precipitates inside the cell (Heinz bodies) and interferes with erythropoiesis, alters cell membrane function and leads to hemolysis and severe anemia.
- The child requires repeated blood transfusions. Iron load increases secondary to multiple transfusions and increased absorption from GI tract due to hypoxia. Iron deposition (hemosiderosis) leads to liver, cardiac and endocrinal dysfunction. Growth is stunted. Hyperplastic bone marrows particularly frontal bossing and maxillary prominence gives typical “Thalassemia facies”. They die early due to intercurrent infections and cardiac failure. Survival beyond teens is uncommon. Also they are infertile due to gonadal dysfunction. So pregnancy with β thalassemia major is rare.
- However with better transfusion facilities and iron chelating therapy (desferioxamine) pregnancy cases have been reported.
- Due to high maternal mortality in such cases MTP is strongly indicated.
- β Thalassemia intermedia:
- This applies to clinical conditions where disease is much less intense than β thalassemia. Major but severe than minor.
- The several possibilities to explain this intermediate condition are coinheritance of OC thalassemia (OCβ thalassemia). HbE β thalassemia, unusual high levels of HbF synthesis and other rare mutations.
- Hemolytic anemia requiring intermittent, but not regular, blood transfusion occurs.
- β Thalassemia minor:
- May be asymptomatic and may go unrecognized during pregnancy.
- Mild microcytic hypochromic anemia which does not respond to iron therapy. In such cases Hb electrophoresis should be advised.
- Diabetes and hypothyroidism are frequently found in these patients.
- Hb remains around 7–8 g% and occasionally blood transfusion may be required.
- Parenteral iron should never be given.
- Mild splenomegaly is common.
- Hb A2 >3.5% by Hb electrophoresis confirms β thalassemia
Different Hbs carry different electrical charges so they can be separated and measured by electrophoresis.- It is important to check the husband's status and if he is also minor, fetus has 1 in 4 (25%) chances of developing β thalassemia major. So prenatal diagnosis of such fetus and termination of pregnancy is advisable for primary prevention of β thalassemia major.
- Prenatal diagnosis is done by fetal DNA analysis from trophoblast obtained by chorionic villi sampling (>10 weeks gestation) or from amniotes obtained by amniocentesis (>15 weeks gestation) direct measuring of the relative amounts of globin chain synthesis can be done in fetal blood. Fetal blood sampling is done by ultrasonography (USG) guided cordocentesis (18–20 weeks) but this carries risk of fetal loss.
- When both the parents are minor, 50% of the fetuses inherit carrier state and 25% will be totally normal.
- Noninvasive prenatal testing (NIPT): This is new technique to diagnose genetic conditions of fetus. Maternal blood sample is taken after 10 weeks of pregnancy. These types of genetic conditions can be diagnosed—(1) aneuploidy, i.e., extra chromosome, e.g., trisomy 21: Down syndrome, (2) microdeletions, i.e., small deletion in a specific region of a chromosome or (3) single gene disease, i.e., genetic conditions caused by mutations in a gene, e.g., beta thalassemia, sickle cell disease.
- In utero stem cell transplantation and gene therapy are under research.
HEMOGLOBIN VARIANTS (SICKLING SYNDROMES)
Unlike thalassemia, here there is structural defect in globin chain, but its rate of synthesis is normal. Hundreds of Hb variants have been described, those affecting beta chain are more common and sickle cell hemoglobin Hb S is the most common.
Hb S is transmitted by autosomal recessive gene. The heterozygous state is called sickle cell trait (Hb AS), while homozygous state is called sickle cell anemia or sickle cell disease (Hb SS).
The exact defect in different Hb variants are described in Table 1.15. Amongst the sickling syndromes major disorders (clinically severe) include—(1) sickle cell anemia (Hb SS); (2) sickle cell C disease (Hb SC) and (3) sickle cell β thalassemia. The last two are combined heterozygous states. Minor disorders, (clinically mild) include sickle cell trait (Hb AS), sickle cell E disease (HB SE). Hb CC and Hb EE even though homozygous are clinically mild hemoglobinopathies.
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Pathophysiology: The name sickle is given because RBCs containing Hb S on deoxygenation assumes the shape of sickle as shown in Figure 1.3.
Hb S is soluble in oxygenated state but in a reduced (deoxygenated) state it gets polymerized (aggregates). This leads to sickle shape of RBC. On oxygenation again DE polymerization occurs. But repeated sickling and DE sickling leads to cell membrane damage and RBC becomes permanently sickled (even in oxygenated state).
The sickle cells are rigid and cannot pass through microcirculation, such as normal RBCs. The blockage of small vessels leads to microinfarcts, painful vaso-occlusive crisis and end organ damage. These abnormal RBCs are filtered in spleen (trapped and destroyed). The life span of such RBCs is hardly 10–20 days (normal 120 days).
In sickle cell anemia (Hb SS) there is no normal Hb A, but in sickle cell trait (Hb AS) >50% is Hb A. So in patients of HB AS clinical manifestations are rare except under conditions of extreme hypoxia. Hb F (α2γ2) has some protective effect to sickling. Hb F present in the same RBC prevents polymerization of Hb S on DE oxygenation and prevents sickling. It is about 2–20% in patients with Hb SS.
Sickle cell trait in pregnancy:
- No effect on pregnancy. Patients may not be aware of the disease due to its asymptomatic nature.
- Patients may have mild anemia (normocytic). Hb usually remains between 7–10 g%.
- Iron and folic acid supplements should be given.
- Urinary tract infection (pyelonephritis) risk is doubled.
- People with sickle cell Hb are immune to malaria as malarial parasites are trapped and killed along with sickled RBCs. This is the reason why sickle cell is common in malarial endemic regions, e.g., Africa. Nature offers protection by causing mutagenic change in the gene for globin chain to produce Hb S.
- If sickle cell trait is diagnosed in mother, counselling is done and husband's Hb is checked for Hb S. If he is also having Hb S trait prenatal diagnosis is offered to couple to detect 25% chances of fetus having sickle cell anemia (Hb SS). Prenatal diagnosis is done as described under thalassemia and if found homozygous state in fetus (Hb SS), MTP is advised.
Sickle cell anemia (Hb SS):
- It is severe condition with variable clinical manifestations. There are no parameters to judge the severity of the disease and frequency of crisis. The disease starts right from childhood, at 3–6 months of age when Hb F is normally replaced by normal Hb A (here Hb SS).
- Chronic hemolytic anemia is present with Hb ranging between 6 to 9 g%.
- Crisis is precipitated by infection, cold, exercise dehydration, acidosis, stress and high altitude.
Different crisis are:
- Painful crisis: Due to vascular occlusion of various organs by capillary thrombosis resulting in infarction. Severe pain can occur in abdomen, chest, back, bones and joints.
- Aplastic crisis: It is not infrequent during pregnancy. It may be due to viral or bacterial infection.
- Hemolytic crisis: Acute hemolysis.
- Megaloblastic crisis: Due to folate deficiency particularly during twin pregnancy.
Treatment of crisis include oxygenation, narcotic analgesics, hydration by intravenous (IV) fluids, antibiotics and blood transfusion (PCV or exchange transfusion to reduce Hb S <30%).
Plasma expanders and anticoagulant (heparin) are not found useful.
Due to repeated microinfarcts patients may have renal damage, chronic lung disease, cardiac dysfunction, retinopathy, bony deformity, and CNS damage and leg ulcers.
Effects of disease on pregnancy:
Maternal:
- Severe anemia: Due to extra burden of pregnancy on a chronic hemolytic state.
- Sickling crisis: Increased, but severity and frequency are unpredictable.
- Pre-eclampsia: Increased incidence (15%). It may be due to placental ischemia and endothelial injury due to sickling.
- Infections: Pyelonephritis, pulmonary infections and puerperal sepsis are more common.
Perinatal:
(1) Abortion, (2) Prematurity, (3) IUGR—due to severe anemia or poor perfusion of placenta, (4) Stillbirth.
Overall perinatal mortality increases by 7 times.
Effects of pregnancy on disease:
As such there is no direct effect, but patients are more likely to have crisis during late pregnancy, delivery and puerperium.
Maternal mortality can be as high as 25%.
Antenatal management:
- Counseling of the patient regarding disease and risk of complications.
- Hematologist should be consulted.
- Frequent antenatal visits: Every 2 weeks in 2nd trimester and every weekly in third trimester.
- Folic acid 5 mg is given to all. Iron is only indicated if deficiency is confirmed.
- Fetal surveillance should begin at 32–34 weeks by serial USG and weekly nonstress tests (NSTs).
Investigations:
- Routine pregnancy investigations.
- Peripheral smear shows normocytic hypochromic RBCs with sickle cells, target cells and increased reticulocyte count.
- Repeated urinalysis, urine culture to detect UTI and asymptomatic bacteriuria.
- Renal function test (RFT) and liver function test (LFT).
- Serum iron is high unless concomitant iron deficiency exists.
- Tests for sickling.
- Sickle test: 1 drop of fresh 2% reagent, such as sodium metabisulfite mixed on a slide with 1 drop of blood. The sickling of red cells is seen when examined after 1 hour.
- Solubility test: It is a simple solubility test that uses 20 mL of blood mixed with 2 mL of sodium dithionite reagent. Clouding of solution indicates the presence of Hb S.
Both above tests are screening tests. They do not differentiate between Hb SS and Hb AS. - Hb electrophoresis confirms Hb SS. Here there is no Hb A and Hb F is about 2–20%
- High performance liquid chromatography (HPLC)5 has an advantage over Hb electrophoresis that it accurately 21identifies and measures abnormal hemoglobins. It is rapid and highly specific and sensitive method.
Prophylactic Blood Transfusions6
- Its role is controversial. It is given every 6 weeks. It may decrease the incidence of crisis, but the obstetric outcome is not altered.
- The risk of transfusion related diseases increase. The development of multiple other antibodies leads to future transfusion problematic. So any transfusion should be after proper checking of all minor RBC antigens and leucocyte poor.
- Some authorities prefer blood transfusion only when need arises, i.e., crisis, severe anemia or in multiple pregnancy.
- The purpose of prophylactic transfusion is to keep Hb around 10–11 g% and Hb S around 30–40%.
Intrapartum
- The patient is managed on the same lines as cardiac patient.
- Continuous oxygen is given.
- Good hydration is ensured if required by IV fluids.
- Prolonged labor and acidosis is avoided by appropriate measures.
- Continuous electronic fetal monitoring is advisable.
- LSCS is done only for obstetric indications. Some patients may have bony deformities.
- Regional (epidural) anesthesia is preferred to GA.
- Proper antibiotic cover is must.
Postpartum
- Breastfeeding is not contraindicated.
- Antibiotics are continued.
Contraception
- Sterilization is advised even with one child due to short life span of the mother.
- Oral pills are contraindicated due to thromboembolic risks. Progesterone only contraceptives can be given.
- IUCD is contraindicated for risk of infection and bleeding.
- Barrier contraceptives are preferred.
- The drugs which increase the HbF level and thereby decrease the risk of sickling are used. These are hydroxyurea, butyrates, recombinant erythropoietin. The first two are antineoplastic drugs. Although no fetal anomalies are reported with their use during pregnancy, they are used with caution.
- Bone marrow transplant during childhood is curative. But it is costly and risky. Intrauterine stem cell transplantation or gene therapy are under research.
IMPORTANT
- Anemia is directly responsible for 15–20% of all maternal deaths and in another same % of deaths it is indirectly involved. Apart from this, maternal morbidity is considerable.
- 1 pint of blood raises Hb by 0.8–1.2 g%.
- 1 g of Hb can combine with 1.34 mL of O2.
- 1 transferrin molecule binds 2 atoms of iron. Total iron bound to transferrin in the blood is 3–4 mg.
- 1 mL of red cells contain 1.1 mg iron.
- Antidote to iron are Desferioxamine and Deferiprone (L1). Desferioxamine is given SC or IV infusion, while Deferiprone (L1) has the advantage of oral route and low cost. Deferasirox is another antidote which can be given orally, but its safety during pregnancy and breastfeeding is not established.
- Kelly-Paterson syndrome or Plummer-Vinson syndrome comprises a triad of dysphagia, iron deficiency anemia and esophageal webs. Patients will also have other symptoms of anemia.
- Advantages of physiological anemia (hemodilution) include—(1) postpartum 22loss of RBCs is reduced, (2) blood viscosity is reduced and (3) increases gaseous exchange at placental level, (4) Overall increase in blood volume copes up with decreased peripheral resistance and increased cardiac output of pregnancy.
- In hemoglobinopathies patients with sickling syndromes have more maternal morbidity and mortality than thalassemia patients.
SPECIAL POINTS
History
- History of worm infestation, malaria, dysentery, piles.
- History suggesting malabsorption syndrome.
- History suggesting hemolytic anemia—hemoglobinopathy.
- History of bleeding from any site.
- Personal history: Diet—vegetarian or nonveg, dietary habits, socioeconomical status.
- Menstrual history: History of menorrhagia.
- Obstetric history: High parity, pregnancies at short intervals, history of PPH in past pregnancy.
Examination
- Pallor of skin and mucous membranes.
- Tongue—glossitis can give false results.
- Conjunctiva—conjunctivitis can give false results.
- Nails—Koilonychia suggests chronic anemia.
- Loss of color of palmar creases suggest severe anemia.
- Edema legs—it may be due to anemia, or it may be physiological. Associated hypoproteinemia or PIH may be the cause.
- Tachycardia
- Hemic murmurs—ejection systolic murmurs.
- Findings symptoms of multiple pregnancy—nutritional anemia is common in multiple pregnancy.
REFERENCES
- NFHS-4—National Family Health Survey. Rchiips.org>NFHS> Factsheet_NFHS-4.
- Thomas S, Srivastava A, Jeyaseelan L et al. NESTROFT as a screening test for the detection of thalassaemia and common hemoglobinopathies—an evaluation against a high performance liquid chromatographic method. Indian J Med Res. 1996;104:194–7.
- Bhavi SB, Jaju PB. Intravenous iron sucrose v/s oral ferrous fumarate for treatment of anemia in pregnancy. A randomized controlled trial. BMC Pregnancy Childbirth. 2017;17:137.
- Jose A, Mahey R, Sharma JB, et al. Comparison of ferric carboxymaltose and iron sucrose complex for treatment of iron deficiency anemia in pregnancy-randomised controlled tr ial. Pregnancy Childbirth. 2019;19(1):54.
- Khera R, Singh T, Khuana N, Gupta N, Dubey AP. HPLC in characterization of hemoglobin profile in thalassemia syndromes and hemoglobinopathies: a clinicohematological correlation. Indian Hematol Blood Transfus. 2015;31(1):110–5.
- Howard J. Sickle cell disease: when and how to transfuse. Hematology Am Soc Hematol Educ Program. 2016;2016(1):625–31.
QUESTIONS
1. What do you mean by physiological anemia during pregnancy? What are its advantages?
2. What are the complications of anemia in second trimester of pregnancy?
3. How will you treat severe anemia during pregnancy at any gestational age?
4. In what different ways blood is given during pregnancy?
5. What are the complications of blood transfusion?
6. Why I/V Inferno is not given nowadays? How will you treat anaphylactic reactions?
7. How will you treat moderate iron deficiency anemia at 16 weeks and at 36 weeks?
8. Which food articles contain good amount of iron?
9. How will you manage anemic patients in labor?
10. In which pregnant patient's anemia and PIH occur together?
12. What are the causes of hypochromic microcytic anemia?
13. What are the causes of megaloblastic anemia?
14. How will you diagnose hookworm infestation? How will you treat them?
15. What are the problems of folic acid deficiency during pregnancy?
16. Why pernicious anemia is not common during pregnancy?
17. What are different oral iron preparations? How are they different?
18. What is hemoglobinopathy? Which are commonly seen during pregnancy? How will you Rx them?
19. What is the relation of anemia and maternal mortality?
20. What is autologous blood transfusion?
21. What are the causes of acute anemia during pregnancy?
22. Which parenteral iron preparations are used now? How will you calculate the dose?