Disorders of Red Blood Cells

Definition

Disorders of the red blood cells (RBCs) are of clinical importance in dental practice for several reasons. First, the dentist serves an important role in detecting patients with previously undiagnosed anemia through history, clinical examination, and the results of screening laboratory tests. These screening procedures should lead to prompt referral to a physician and the establishment of the diagnosis. Clinical recognition of anemia can significantly affect morbidity and mortality risks because anemia often occurs as an underlying condition that requires attention and medical treatment. Also, anemia is an independent risk factor for adverse cardiovascular outcomes (i.e., acute myocardial infarction and death) in a variety of patient populations (as defined by chronic kidney disease, acute coronary syndrome, or old age).

Anemia, which is defined as a reduction in the oxygen-carrying capacity of the blood, is usually associated with a decreased number of circulating RBCs or an abnormality in the hemoglobin (Hb) contained within the RBCs ( Fig. 22.1 ). Anemia is not a disease but rather a symptom complex that may result from one of three underlying causes: (1) decreased production of RBCs (iron deficiency, folate deficiency, pernicious anemia), (2) blood loss, or (3) increased rate of destruction of circulating RBCs (hypersplenism, autoimmune destruction).

FIG 22.1
Relative frequencies of anemia in clinical practice.
(Redrawn from Hillman RS, Finch CA, editors: Red cell manual, ed 7, Philadelphia, 1996, FA Davis.)

Oxygen demand (hypoxia) serves as the stimulus for erythropoiesis (RBC production). The kidney serves as the primary sensor for determining the level of oxygenation. If the level is low, the kidney releases erythropoietin, a hormone that stimulates the bone marrow to release RBCs. Hb, the oxygen-carrying molecule of RBCs, consists of two pairs of globin chains (i.e., α plus β, δ, or γ) that form a shell around four oxygen-binding heme groups. The normal RBC is about 33% Hb by volume.

COMPLICATIONS: Anemia increases the risk for acute myocardial infarction, chronic kidney disease, acute coronary syndrome, and death. Pernicious anemia is associated with increased risk of gastric carcinoma. Sickle cell anemia is associated with increased risk of stroke, infection, osteonecrosis of the hip and shoulder joints, liver disease, hypertension, and sudden death from arrhythmias. Aplastic anemia is associated with bleeding issues, infection, and death.

Types of Anemia

Iron Deficiency Anemia

Iron deficiency anemia is a microcytic anemia ( Fig. 22.2 ) that can be caused by excessive blood loss, poor iron intake, poor iron absorption, or increased demand for iron.

FIG 22.2
Microcytic anemia associated with iron deficiency. Peripheral blood smear shows red blood cells that are small and have marked hypochromic central pallor.

Folate Deficiency Anemia and Pernicious Anemia

Vitamin B 12 (cobalamin) and folic acid are needed for RBC formation and growth within bone marrow. A deficiency in daily intake or absorption of these vitamins can result in anemia.

Hemolytic Anemia

Hemolytic anemias consist of sickle cell anemia, thalassemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. They are commonly caused by immune attack, extrinsic factors (infection, splenomegaly, drugs, eclampsia), disorders of the RBC membrane (spherocytosis), enzymopathies, and hemoglobinopathies.

Sickle Cell Anemia

The two most common types of sickle cell disorders are sickle cell trait and sickle cell (disease) anemia. Sickle cell trait is the heterozygous state in which the affected person carries one gene for sickle cell hemoglobin (HbS), the result of substitution of a single amino acid—valine for glutamic acid—at the sixth residue of the β-hemoglobin chain. In patients with sickle cell anemia, more than 80% of the Hb is HbS. In contrast, the thalassemias, another type of hemoglobinopathy, are caused by deletions or mutations of the α- or β-globin gene that result in a defect in globin synthesis (reduced or absent synthesis of one or more globin chains).

Glucose-6-Phosphate Dehydrogenase Deficiency

Glucose-6-phosphate dehydrogenase is an enzyme that enables the RBC to convert carbohydrates into energy via the hexose monophosphate shunt pathway. Blockade of this enzymatic pathway in persons with G6PD deficiency allows for production of methemoglobin and denatured Hb, which leads to cell membrane alterations andhemolysis of the cell (hemolytic anemia).

Aplastic Anemia

Aplastic anemia occurs when the bone marrow is unable to produce adequate numbers of RBCs, white blood cells (WBCs), and platelets because of an inability of the hematopoietic stem cells to proliferate, differentiate, or give rise to mature blood cells.

Types of Anemia

Iron Deficiency Anemia

Iron deficiency anemia is a microcytic anemia ( Fig. 22.2 ) that can be caused by excessive blood loss, poor iron intake, poor iron absorption, or increased demand for iron.

FIG 22.2
Microcytic anemia associated with iron deficiency. Peripheral blood smear shows red blood cells that are small and have marked hypochromic central pallor.

Folate Deficiency Anemia and Pernicious Anemia

Vitamin B 12 (cobalamin) and folic acid are needed for RBC formation and growth within bone marrow. A deficiency in daily intake or absorption of these vitamins can result in anemia.

Hemolytic Anemia

Hemolytic anemias consist of sickle cell anemia, thalassemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. They are commonly caused by immune attack, extrinsic factors (infection, splenomegaly, drugs, eclampsia), disorders of the RBC membrane (spherocytosis), enzymopathies, and hemoglobinopathies.

Sickle Cell Anemia

The two most common types of sickle cell disorders are sickle cell trait and sickle cell (disease) anemia. Sickle cell trait is the heterozygous state in which the affected person carries one gene for sickle cell hemoglobin (HbS), the result of substitution of a single amino acid—valine for glutamic acid—at the sixth residue of the β-hemoglobin chain. In patients with sickle cell anemia, more than 80% of the Hb is HbS. In contrast, the thalassemias, another type of hemoglobinopathy, are caused by deletions or mutations of the α- or β-globin gene that result in a defect in globin synthesis (reduced or absent synthesis of one or more globin chains).

Glucose-6-Phosphate Dehydrogenase Deficiency

Glucose-6-phosphate dehydrogenase is an enzyme that enables the RBC to convert carbohydrates into energy via the hexose monophosphate shunt pathway. Blockade of this enzymatic pathway in persons with G6PD deficiency allows for production of methemoglobin and denatured Hb, which leads to cell membrane alterations andhemolysis of the cell (hemolytic anemia).

Aplastic Anemia

Aplastic anemia occurs when the bone marrow is unable to produce adequate numbers of RBCs, white blood cells (WBCs), and platelets because of an inability of the hematopoietic stem cells to proliferate, differentiate, or give rise to mature blood cells.

Epidemiology

It is estimated that anemia affects 1.62 billion people globally and 3.4 million Americans, with the highest prevalence in young children. Approximately 4% of men and 8% of women in the United States have anemia, defined as Hb values below 13 g/dL for men and below 12 g/dL for women. In the United States, iron deficiency anemia is the most common type. Folate deficiency anemia occurs in about 4 of 100,000 people. The sickle cell trait is carried by approximately 8% to 10% of African Americans. In western Africa, 25% to 30% of the population may be carriers. Approximately 50,000 African Americans (≈0.003%–0.15%), or 1 in 600, have sickle cell anemia. If contemporary health care is not provided, 50% of persons with sickle cell anemia will die before the age of 30 years; however, because of advances in medical care, sickle cell anemia is now considered a chronic adult disease. The incidence of aplastic anemia in the United States is about 2 cases per 1 million persons per year. The incidence is about two times higher in Asia. Of the approximately 2000 patients treated in the average dental practice, about 12 men and 24 women will be anemic. In most of these patients, the condition may be undiagnosed.

Etiology

Anemia has numerous causes, including genetic disorders that produce aberrant RBCs that result in RBC destruction (hemolysis), nutritional disorders that limit the production of RBCs, immune-mediated disorders that result in attacks on RBCs, bleeding disorders that cause loss of RBCs, chronic diseases (e.g., rheumatoid arthritis), infections, and diseases of bone marrow ( Table 22.1 ).

TABLE 22.1
Types of Anemia
Classification by RBC Size and Shape Cause
MICROCYTIC (MCV ≤80 FL * )
Iron deficiency anemia Decreased production of RBCs
Thalassemias Defective hemoglobin synthesis
Lead poisoning Inhibition of hemoglobin synthesis
NORMOCYTIC (MCV 80–100 FL * )
Hemolytic anemia

  • Sickle cell anemia

  • G6PD deficiency

Increased destruction of RBCs
Aplastic anemia Decreased production of RBCs
Renal failure Decreased production of RBCs
Anemia of chronic disease Decreased production of RBCs
MACROCYTIC (MCV >100 FL * )
Pernicious anemia Decreased production of RBCs
Folate deficiency Decreased production of RBCs
Hypothyroidism Decreased production of RBCs
fL, Femtoliter; G6PD, glucose-6-phosphate dehydrogenase; MCV, mean corpuscular volume; RBC, red blood cell.

* Also expressed in µm 3 units.

Pathophysiology and Complications

Iron Deficiency Anemia

Depletion of iron commonly occurs with blood loss caused by menstruation, pregnancy, or bleeding from the gastrointestinal (GI) tract. During pregnancy, the expectant mother experiences an increased demand for additional iron and vitamins to support the growth of her fetus, and unless sufficient amounts of these nutrients have been provided in some form, she may become anemic. Anemia in men usually indicates the presence of a serious underlying medical problem (e.g., GI bleeding, malignancy). Poor intake is more common in children who live in developing countries, where cereals and formula fortified with iron are not readily available. Malabsorption of iron can result from gastrectomy or intestinal disease that reduces absorption of iron from the duodenum and the jejunum. Increased demand is associated with chronic inflammation (autoimmune disease).

Folate Deficiency and Pernicious Anemia

Vitamin B 12 (cobalamin) and folic acid are needed for RBC formation and growth within bone marrow. Vitamin B 12 is a cofactor in methionine-associated enzymatic reactions required of protein synthesis and thus in the maturation of RBCs. Folate is needed for enzymatic reactions required for the synthesis of purines and pyrimidines of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and thus for the synthesis of proteins. Risk factors for folate deficiency include poor diet (frequently encountered in poor individuals, older adults, and people who do not eat fresh fruits or leafy vegetables), alcoholism, history of malabsorption disorders, and pregnancy (especially during the third trimester).

Pernicious anemia is caused by a deficiency of intrinsic factor, a substance secreted by the gastric parietal cells that is necessary for absorption of vitamin B 12 . Most patients with pernicious anemia have chronic atrophic gastritis with decreased intrinsic factor and hydrochloric acid secretion. Antibodies against parietal cells and intrinsic factor also are present in the sera of most patients. This finding strongly suggests that the disease is of autoimmune origin. Long-standing pernicious anemia is associated with increased risk for development of gastric carcinoma. In addition, an association with myxedema, rheumatoid arthritis, and neuropsychiatric and neuromuscular abnormalities (caused by a defect in myelin synthesis) has been reported.

Sickle Cell Anemia

Sickle cell hemoglobin is the result of substitution of a single amino acid—valine for glutamic acid—at the sixth residue of the β chain. Sickle cell disorders are distinguished by the number of globin genes affected. Whereas sickle cell trait is the heterozygous state in which the affected person carries one gene for HbS, sickle cell anemia is the homozygous state. In patients with sickle cell anemia, more than 80% of the Hb is HbS. Distortion of the RBC into a sickled shape results from deoxygenation or decreased blood pH, causing partial crystallization of HbS, polymerization, and realignment of the defective Hb molecule ( Fig. 22.3 ). Cellular rigidity and membrane damage occur, and irreversible sickling is the result. The net effects of these changes are erythrostasis, increased blood viscosity, reduced blood flow, hypoxia, increased adhesion of RBCs, vascular occlusion, and further sickling.

FIG 22.3
Sickle cell anemia. Peripheral blood smear shows characteristic abnormal sickle-shaped red blood cells.

Complications of sickle cell anemia can occur at any age, but patients in the following age groups are more likely to manifest certain complications:

  • 1.

    Birth to 20 years of age: painful events, stroke, acute chest syndrome (fever, chest pain, wheezing, cough, and hypoxia), acute anemia, and infection

  • 2.

    From 20 to 40 years of age: osteonecrosis of hip and shoulder joints, leg ulcers, priapism, liver disease, and gallstones

  • 3.

    Older than 40 years of age: pulmonary hypertension, nephropathy, proliferative retinopathy, and cardiac enlargement, heart murmurs, and sudden death from arrhythmias

Clinical Presentation

Signs and Symptoms

Symptoms of anemia occur in proportion to the rate of development of anemia; rapidly developing anemia has more profound features than slowly developing anemia. Because anemia develops slowly in most affected patients, few symptoms are typically experienced until the condition worsens. Usual symptoms include fatigue, lethargy, palpitations, shortness of breath, abdominal pain, bone pain, tinnitus, irritability, dizziness, tingling of fingers and toes, and muscular weakness. Specific to iron deficiency anemia are impaired immunity and resistance to infection and diminished exercise tolerance and work performance. Clinical features of G6PD deficiency involve acute intravascular hemolysis, which may be severe. Jaundice, palpitations, dyspnea, and dizziness may result. Clinical signs and symptoms of sickle cell anemia include jaundice, pallor, dactylitis (hand and foot warmth and tenderness), leg ulcers, organomegaly, cardiac failure, stroke, attacks of abdominal and bone pain (aseptic necrosis), and delays in growth and development ( Fig. 22.4 ). The most common initial signs and symptoms of aplastic anemia are weakness, fatigue, headaches, dyspnea with exertion, petechiae, ecchymoses, epistaxis, metrorrhagia (bleeding between expected menstrual periods), and gingival bleeding. Infection is rare as an initial presentation, even in cases of severe neutropenia.

FIG 22.4
Sickle cell anemia may cause various complications. A, Leg ulcer secondary to a vasoocclusive attack. B, Growth deformation of the middle finger from dactylitis of the growth plate.
(From Hoffbrand AV, Pettit JE: Color atlas of clinical hematology, ed 4, London, 2010, Mosby.)

Signs of anemia may include jaundice; pallor; cracking, splitting, and spooning of the fingernails; increased size of the liver and spleen; lymphadenopathy; and blood in the stool. Premature graying of hair and yellowing of the skin (caused by jaundice) have been reported with pernicious anemia ( Fig. 22.5 ). Patients with anemia also may describe a sore or painful tongue (glossitis), a smooth tongue, or redness of the tongue or cheilosis ( Fig. 22.6 ). Some patients may complain of loss of taste sensation.

FIG 22.5
Pernicious anemia. This 38-year-old woman has blue eyes and vitiligo and shows premature graying of the hair—three features that are more common in patients with pernicious anemia than in control subjects.
(From Hoffbrand AV, Pettit JE: Color atlas of clinical hematology, ed 4, London, 2010, Mosby.)

FIG 22.6
Smooth red tongue and angular cheilitis in a patient found to have iron deficiency anemia.

Laboratory and Diagnostic Findings

A patient with signs or symptoms suggestive of anemia should be sent to a commercial laboratory for a complete blood count and differential or referred to a physician for evaluation. Hb level, hematocrit, and RBC indices (mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], RBC distribution width [RDW], and mean corpuscular hemoglobin concentration [MCHC]) are tests that are used to screen the patient. In addition, total WBC count and platelet count should be obtained to determine whether a generalized bone marrow defect has occurred and to evaluate for hypersegmented neutrophils (see Chapter 23 ).

Anemia is generally defined as Hb level less than 12 g/dL for women and less than 13 g/dL for men. In accordance with the size of RBCs, anemia is classified as microcytic (MCV <80 fL [or µm 3 ]), macrocytic (MCV >100 fL), or normocytic (MCV of 80–100 fL). Whereas a reticulocyte count (based on percentage of RBCs) of less than 0.5% indicates inadequate RBC production in the bone marrow, a value greater than 1.5% indicates increased production in response to bleeding or destruction. Based on the absolute reticulocyte count in the presence of anemia, a value below 75,000/µL indicates hypoproliferative anemias, and a value greater 100,000/µL indicates hemolysis or an appropriate erythropoietic response. To distinguish between the various types of anemias, key laboratory tests, as shown in Table 22.2 , are performed.

Sep 3, 2018 | Posted by in General Dentistry | Comments Off on Disorders of Red Blood Cells
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