Anemia and Hemoglobinopathies
Among the most common complaints of women seeking care is the familiar “I’m tired all the time, I must be anemic.” While there are many causes of fatigue—from anemia to thyroid disease to stress—
this one is the first focus of concern for many women. Signs and symptoms associated with ane- mia are listed in Table 7-3.
In addition to these, the history and review of systems should include an assessment of menstrual flow, even though women’s estimation of their flow has been demonstrated to be inaccurate [12]. Prior diagnosis of anemia merits a description of the cir- cumstances. For example, some women may have been treated for pregnancy-related anemia and be- lieve that they will therefore always be anemic.
The diets of most Americans, with the exception of some vegetarians, include about 15 mg of iron daily, and about 10 percent of that is absorbed.
Normal daily iron loss through excretion, sweat, and cellular shedding amounts to 1 mg; the menses add an additional monthly loss which, with pregnancy- Screening
Blood pressure, height, and weight:Periodically, ages 18–75
Cholesterol: Men, every 5 years, ages 35–75 Women, every 5 years, ages 45–75 Pap smear:Women, every 1–3 years, ages 18–65 Chlamydia:Women, periodically, ages 18–25 Mammography:Women, every 1–2 years, ages 40–75 Sigmoidoscopy:Every 5 years, ages 50–75
And/or fecal occult blood:Yearly, ages 50–75 Alcohol use:Periodically, ages 18–75
Vision, hearing:Periodically, ages 65–75 Immunization
Tetanus-diphtheria (Td):Every 10 years, ages 18–75 Varicella (VZV):Susceptibles only, two doses, ages 18–75 Measles, mumps, rubella (MMR):Women of childbearing
age, one dose, ages 18–50
Pneumococcal:One dose, ages 65–75 Influenza:Yearly, ages 65–75 Chemoprevention
Aspirin to prevent cardiovascular events:
Men, periodically, ages 40–75 Women, periodically, ages 50–75 Counseling
Calium intake:Women, periodically, ages 18–75 Folic acid:Women of childbearing age, ages 18–50 Tobacco cessation, drug and alcohol use, STDs and HIV,
nutrition, physical activity, sun exposure, oral health, injury prevention, and polypharmacy:
Periodically, ages 18–75
Source: Clinical Preventive Services for Normal Risk Adults Recommended by the U.S. Preventive Services Task Force. Put Prevention into Practice, Rockville, MD: Agency for Health Care Quality and Research, June 2002.
Symptoms and Signs Associated with Significant Anemia
TABLE 7-3
Symptoms
Fatigue, drowsiness Weakness
Dizziness Headaches Malaise Pica
Poor appetite, changes in food preferences Changes in mood
Changes in sleep habits Signs
Pallor Jaundice
Orthostatic hypotension Peripheral edema
Pale mucous membranes and nail beds Smooth, sore tongue
Splenomegaly
Tachycardia or flow murmur Tachypnea, dyspnea on exertion
related demands, increases the daily iron need among reproductive age women to 2 to 3 mg/day [13].
A complete blood count (CBC) offers the first level of assessment and will differentiate many of the underlying causes of anemia. Defined as a de- crease in red blood cell mass, or more correctly in total hemoglobin, the normal hemoglobin level for menstruating women is 12.0, and for pregnant women it is 11.0 g/dL [14]. However, no adverse ef- fects are expected unless the level is <10.0 g/dL [15]. The U.S. Department of Health and Human Services does not recommend screening for anemia as part of routine health care for adults, except among pregnant women [16].
There are a number of confounding factors.
Economic status has an effect, in that lower status translates into higher rates of poor nutrition and thus a higher rate of iron deficiency anemia. Race plays a role; for example, Blacks average about 1 g/dL lower hemoglobin levels than Whites regard- less of socioeconomic level. Women who smoke (because of competition for oxygen-binding sites on red blood cells) and women living at high altitudes (because of lower oxygen concentration in the at- mosphere) demonstrate higher hemoglobin and hematocrit levels as their bodies adapt to maintain adequate oxygenation (see Tables 7-4 and 7-5) [17].
Identifying the cause of decreased hemoglobin will lead to appropriate therapy and in some cases to referral to a specialist. One way to classify anemias is by the size of the red blood cells. Microcytic ane- mias include iron deficiency, the thalassemias, and anemia of chronic disease. Macrocytic anemias in- clude folate and vitamin B12deficiency, liver disease, increased reticulocyte production, and some effects from medication—for example, from zidovudine (Retrovir). Normocytic anemias commonly reflect acute blood loss or conditions such as sickle cell dis- ease, hemoglobin C, or G6PD. Aplastic anemia, while normocytic, shows pancytopenia. Table 7-6
presents the laboratory values associated with some common anemias. When the hemoglobin is below 10.0 g/dL, a laboratory panel including the CBC, serum folate, serum iron, ferritin, and total iron binding capacity should be ordered, and a hemoglo- bin electrophoresis performed. Based on the severity of the anemia and its cause, consultation or referral may be indicated. When the hemoglobin indicates severe anemia (<9.0 g/dL) consultation is always ap- propriate, even if the anemia is clearly caused by iron deficiency.
Smoking Adjustments for Hemoglobin and Hematocrit Cut-Points for Anemia TABLE 7-4
Smoking Status Hemoglobin (g/dL) Hematocrit (%)
Nonsmoker 0.0 0.0
Smoker (all) +0.3 +1.0
0.5 < 1 ppd +0.3 +1.0
1.0–2.0 ppd +0.5 +1.5
>2.0 ppd +0.7 +2.0
Source:From Centers for Disease Control. Reference criteria for ane- mia screening. MMWR Morb. Mortal. Wkly. Rep. 38:400–404, 1989.
Altitude Adjustments for Hemoglobin and Hematocrit Cut-Points for Anemia TABLE 7-5
Altitude (ft) Hemoglobin (g/dL) Hematocrit (%)
<3000 0.0 0.0
3000–3999 +0.2 +0.5
4000–4999 +0.3 +1.0
5000–5999 +0.5 +1.5
6000–6999 +0.7 +2.0
7000–7999 +1.0 +3.0
8000–8999 +1.3 +4.0
9000–9999 +1.6 +5.0
>10,000 +2.0 +6.0
Source:From Centers for Disease Control. Reference criteria for ane- mia screening. MMWR Morb. Mortal. Wkly. Rep. 38:400–404, 1989.
Laboratory Values in Common Anemias TABLE 7-6
Laboratory Test Iron Deficiency Vitamin B12Deficiency Folate Deficiency Thalassemia Chronic Disease
RBC low high high normal normal
Hemoglobin low low low low low
MCV low high high low normal-low
MCH low high high low low
MCHC low normal normal low normal-low
Iron low high high high low
TIBC high normal normal normal low
Ferritin low high high high normal-high
Iron Deficiency
The single most common anemia in the United States is iron deficiency, which in most cases is mild and easily reversible. Occult blood loss, excessive menstrual loss, and inadequate nutritional intake are by far the most common causes in adults. In the absence of an identifiable source of bleeding, as- sessment for gastrointestinal bleeding is warranted;
the midwife should inquire about use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs).
Nutritional deficiencies causing significant iron de- pletion include restrictive vegetarian diets as well as pica, and a careful diet history is part of the workup. Iron supplementation, either nutritional or with oral medications, should be begun in all cases when the hemoglobin is less than 10.0 g/dL. Adding 1.0 mg of folic acid in cases where the serum folate is low or using a vitamin C–enriched product to fa- cilitate absorption may also be useful. Nutritional counseling should stress the importance of includ- ing iron-rich foods in the diet—such as green leafy vegetables, collard greens, egg yolks, raisins, prunes, liver, oysters, and some fortified cereals—as well as the elimination of picas, such as eating ice or nonfood starches. When uncomplicated iron defi- ciency is the cause of the anemia and oral medica- tions are used, any of several iron preparations, including ferrous sulfate, ferrous fumarate, and fer- rous gluconate, can be used. The equivalent of 300 mg of ferrous sulfate taken three times a day is stan- dard. Taking iron preparations with meals will de- crease absorption, but it will also improve gastrointestinal side effects such as nausea and re- flux. After the hemoglobin level has returned to normal, continued supplementation for three months should adequately replenish iron stores in the body.
Thalassemia
Thalassemias are mendelian recessive inherited dis- orders of the globin chains that form normal adult hemoglobin (hemoglobin A). In alpha thalassemias, decreased hemoglobin aproduction causes normal proportions of hemoglobins A, A2, and F. The beta thalassemias show increases in hemoglobins A2and F relative to hemoglobin A on electrophoresis.
Alpha thalassemia is most common among those of Chinese and Southeast Asian descent. Beta tha- lassemia is most common among women of Mediterranean origin, less so among Chinese, Asian, and African women. In both cases, the trait will appear as a microcytic anemia in which the mean cell volume (MCV) is markedly low relative
to the hemoglobin level [18]. A handy shortcut to identifying these traits is Mentzer’s index:
MCV/RBC < 13. Nonetheless, a complete anemia panel is justified to rule out a combination of iron deficiency and hemoglobinopathy. When the diag- nosis is established, folic acid supplementation may be desirable but iron therapy is inappropriate, as supplementation will not resolve the problem. A woman with a hemoglobinopathy needs to under- stand her diagnosis to avoid unnecessary testing in the future and to ensure that before she becomes pregnant she and her partner will be evaluated to decrease the risk of bearing a child with severe he- molytic syndromes such as thalassemia major whose risks for the fetus include hydrops fetalis.
Sickle Cell Disease
Sickle cell trait (hemoglobin AS) is found in about 8 percent of African Americans; although the trait it- self does not cause severe health complications, identification of those carrying the sickle trait is im- portant to enable couples planning children to ob- tain appropriate genetic counseling and testing.
Midwives can care for women with sickle trait. The primary complication is an increase in urinary tract infections and hematuria.
Sickle cell disease (homozygous SS disease) is a recessive inherited disorder in which hemoglobin S is produced instead of hemoglobin A. Repeatedly stressed red blood cells form a permanent crescent moon or “sickle” shape; they may then clump and block the microvasculature. Sickle cell crises involve acute episodes of severe pain from ischemia and in- farction of tissue and organs. The disease has a mul- tiorgan effect and is associated with a shortened life span as a consequence of renal damage, cardiac damage, infection, and acute chest syndrome.
Hemoglobin S may also be present in heterozy- gous SC disease or sickle thalassemia, conditions that lead to somewhat milder forms of sickle crisis.
For all these disease conditions, genetic counseling for couples planning a child is appropriate.
Pregnant women with these diseases should be cared for by a midwife only in close collaboration with a physician experienced in the management of sickle cell disease.
G6PD Deficiency
Glucose-6-phosphate dehydrogenase (G6PD) defi- ciency is an X-linked genetic disease seen in those of Mediterranean descent and in African Americans.
(Being X-linked, it is far more common among men than women.) Hemolysis occurs when the individ-
ual has an infection or receives oxidative drugs.
Certain medications commonly used in pregnancy and women’s health care that must not be given to individuals with G6PD deficiency include sulfa and sulfa derivatives, nitrofurantoin, toluidine blue, and methylene blue. Fava beans will also produce he- molysis in those with the Mediterranean variant.
The management of care of women with G6PD deficiency includes avoidance of substances that may cause hemolysis. Prompt diagnosis and treat- ment of any infection will minimize the risk of he- molysis from infection. Surgery can also precipitate an episode of hemolysis. Therefore, the midwife should remind a woman to notify her surgeon and surgical team prior to any elective or required sur- gery. Genetic counseling and prenatal diagnostic testing should be offered to all women with G6PD deficiency. When caring for a pregnant woman with G6PD deficiency, the midwife should notify the consulting physician so that appropriate care can be provided in the event an operative delivery is needed or the woman requests postpartum surgical sterilization.
Von Willebrand’s Disease
Von Willebrand’s disease is an autosomal dominant mutation causing defects in a polymer necessary for platelet adhesion. It is a leading cause of menorrha- gia, underlying up to 20 percent of cases, particu- larly among teenagers [19–21]. Bleeding disorders should be suspected if the history a woman de- scribes includes heavy menstrual bleeding in associ- ation with increased bruising, nosebleeds, or a family history of bleeding problems. At that point, the midwife should obtain a platelet count and bleeding time and coagulation studies. If the platelets are normal and the bleeding time is pro- longed, von Willebrand’s disease is a strong possi- bility. As with any other bleeding abnormality, the midwife should refer the woman to a hematologist for evaluation, although it would be appropriate for the midwife to continue to provide general care.
The woman should be advised to avoid aspirin if a diagnosis of von Willebrand’s disease is made [18].