III. Laboratory Tests

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The primary manifestations of iron-deficiency anemia include melena, hematochezia, or abdominal discomfort caused by peptic ulcers, tumors, or hemorrhoids; abdominal pain or changes in stool characteristics due to intestinal parasitic infections; excessive menstrual bleeding in women caused by uterine fibroids and other conditions; wasting associated with neoplastic diseases; and hemoglobinuria resulting from intravascular hemolysis. Common symptoms of anemia include fatigue, easy tiredness, dizziness, headache, blurred vision, tinnitus, palpitations, shortness of breath, and loss of appetite, as well as pallor of the skin and mucous membranes and increased heart rate.

Signs of tissue iron deficiency include psychiatric and behavioral abnormalities such as irritability,易怒, difficulty concentrating, pica; decreased physical strength and endurance; increased susceptibility to infection; growth and developmental delays and intellectual impairment in children; stomatitis, glossitis, atrophy of the lingual papillae, angular cheilitis, and dysphagia; dry and brittle hair; dry and wrinkled skin; lack of luster and brittleness of fingernails and toenails, with severe cases showing flattening or even spoon-shaped deformity (koilonychia).

III. Laboratory Tests (1) Hematological findings: Microcytic hypochromic anemia. (2) Bone marrow examination: Active or markedly active proliferation, predominantly erythroid hyperplasia, with no obvious abnormalities in the granulocytic or megakaryocytic lineages; among the erythroid cells, intermediate and late normoblasts predominate, characterized by small cell size, dense nuclear chromatin, scanty cytoplasm, irregular margins, and poor hemoglobin synthesis—referred to as the "nuclear mature, cytoplasm immature" phenomenon. (3) Iron metabolism: Decreased serum iron, increased total iron-binding capacity; reduced transferrin saturation and serum ferritin levels. Prussian blue staining of bone marrow smears reveals no deep-blue hemosiderin granules in the bone marrow sideroblasts, with fewer or absent iron granules within the erythroblasts and a reduction in sideroblasts. (4) Abnormal porphyrin metabolism in red blood cells: Free erythrocyte protoporphyrin (FEP) > 0.9 μmol/L (whole blood), zinc protoporphyrin (ZPP) > 0.96 μmol/L (whole blood), and free erythrocyte protoporphyrin to hemoglobin ratio > 4.5 g/g Hb. (5) Serum transferrin receptor measurement: Currently the best indicator of iron-deficiency erythropoiesis, with concentrations generally > 26.5 nmol/L (2.25 g/mL) suggesting iron deficiency. IV. Diagnosis and Differential Diagnosis (---) Diagnosis (1) Depletion of body iron stores (ID): ① Serum ferritin < 12 μg/L; ② Bone marrow iron staining shows disappearance of stainable iron in the marrow sideroblasts, with sideroblasts accounting for less than 15%; ③ Hemoglobin and serum iron levels are still normal. (2) Intracellular iron deficiency (IDE): ① Combine ID's ① and ②; ② Transferrin saturation < 15%; ③ Free erythrocyte protoporphyrin to hemoglobin ratio > 4.5 g/g Hb; ④ Hemoglobin levels remain normal. (3) Iron-deficiency anemia (IDA): ① Combine IDE's ①, ②, and ③; ② Microcytic hypochromic anemia. Male hemoglobin < 120 g/L, female hemoglobin < 110 g/L, pregnant women hemoglobin < 100 g/L; mean corpuscular volume < 80 fL; mean corpuscular hemoglobin < 27 pg; mean corpuscular hemoglobin concentration < 32%. (4) Etiological diagnosis: IDA is merely a clinical manifestation, often concealing underlying diseases. Only by identifying the root cause can IDA be effectively cured. (II) Differential Diagnosis (should be distinguished from microcytic anemia) (1) Sideroblastic anemia: A hereditary or idiopathic disorder of red blood cell iron utilization. It presents as microcytic anemia, but with elevated serum ferritin levels, increased iron-containing hemosiderin granules in the bone marrow, more sideroblasts, and the appearance of ringed sideroblasts. Serum iron and iron saturation are elevated, and total iron-binding capacity is not low. (2) Thalassemia: Formerly known as Mediterranean anemia, it has a family history and exhibits hemolytic features. Blood smears show numerous abnormal red blood cells, along with evidence of abnormal globin chain synthesis. Serum ferritin, bone marrow-stainable iron, serum iron, and iron saturation are all normal or even elevated. (3) Chronic disease-related anemia: Anemia caused by chronic inflammation, infection, or tumors leading to iron metabolism disorders. (4) Transferrin deficiency: Caused by autosomal recessive inheritance (congenital) or secondary to severe liver disease or tumors (acquired). V. Treatment The principle of treating IDA is to eliminate the underlying cause and replenish iron stores. 1. Etiological treatment: Remove the causative factors of iron deficiency as much as possible. For example, IDA caused by nutritional deficiencies in infants, adolescents, and pregnant women should improve their diet; IDA due to excessive menstrual bleeding should regulate menstruation; patients with parasitic infections should receive anthelmintic treatment; malignant tumor patients should undergo surgery or radiotherapy/chemotherapy; those with peptic ulcers should receive acid-suppressing therapy, etc. 2. Iron supplementation: Therapeutic iron preparations include ferrous sulfate, dextran iron, ferrous gluconate, sorbitol iron, ferrous fumarate, ferrous succinate, and polysaccharide iron complexes, among others. Oral iron supplements are preferred. Note that consuming cereals, dairy products, and tea can inhibit iron absorption, while fish, meat, and vitamin C can enhance it. The effectiveness of oral iron supplements is first manifested by an increase in peripheral reticulocyte counts, peaking 5–10 days after starting medication, followed by a rise in hemoglobin levels after about two weeks, typically returning to normal within approximately two months. Iron supplementation should continue for at least 4–6 months after hemoglobin levels return to normal, and be discontinued only when serum ferritin levels normalize. If oral iron cannot be tolerated or if gastrointestinal anatomy changes affecting iron absorption, intramuscular iron injections may be used, with dextran iron being the most commonly used injectable form. Nutritional care should be emphasized in the treatment of iron-deficiency anemia in infants, adolescents, and women. VI. Professor Pei Zhengxue’s Experience in Diagnosing and Treating Iron-Deficiency Anemia (---) Professor Pei Zhengxue’s Understanding of This Disease This disease falls under categories such as “Xulao,” “Chongbing,” and “Weihuang” in traditional Chinese medicine. The “Suwen · Tongping Xushi Lun” states: “When pathogenic factors are strong, there is excess; when vital energy is depleted, there is deficiency.” The “Suwen · Yujizhenzang Lun” says: “Fine pulse, cold skin, insufficient qi, diarrhea before and after defecation, inability to eat—these are the ‘five deficiencies.’” The “Nanjing · Shisi Nan” states: “One deficiency affects the skin and hair—skin gathers and hair falls out; two deficiencies affect the blood vessels—blood is deficient and cannot nourish the five zang and six fu organs; three deficiencies affect the muscles—muscles become thin and food cannot nourish the skin; four deficiencies affect the tendons—tendons become slack and cannot support themselves; five deficiencies affect the bones—bones become weak and cannot get out of bed. Those who go against this order will develop pulse-related illnesses. Those who start from the top down—bones becoming weak and unable to get out of bed—will die; those who start from the bottom up—skin gathering and hair falling out—will die.” The “Jingyue Quanshu · Xusun” also says: “All causes of deficiency... ultimately stem from alcohol, sexual indulgence, overwork, and emotional disturbances or dietary habits. Therefore, either qi is damaged first, and then the damage spreads to the essence; or the essence is damaged first, and then the damage spreads to the qi.” (II) Professor Pei Zhengxue’s Understanding of the Etiology and Pathogenesis of This Disease Professor Pei Zhengxue believes this disease is mainly related to spleen and stomach weakness, bleeding, and parasitic accumulation. (1) Spleen and stomach weakness: The spleen and stomach have the function of transforming food and water into vital energy, which is then converted into blood. As stated in the “Lingshu · Jueqi” chapter: “The middle jiao receives qi and extracts juice, which transforms into red, thus becoming blood.” If dietary habits are irregular and the spleen and stomach are damaged, they cannot transform food and water, leading to insufficient source of blood production and causing anemia. (2) Bleeding: Frequent and recurrent bleeding, such as metrorrhagia, hematemesis, hematochezia, and hematuria, can deplete qi and blood, resulting in anemia. (3) Parasitic accumulation: Parasites reside in the gastrointestinal tract, sucking up the essence of food and water, thereby reducing the source of blood production and causing anemia. (III) Professor Pei Zhengxue’s Clinical Experience in Treating This Disease

1. Spleen and stomach qi deficiency Manifestations: Pale or yellowish complexion, fatigue, poor appetite and bowel movements, pale tongue, thin and greasy coating, and fine pulse. This type is commonly seen in individuals who are picky eaters or have inherent spleen and stomach weakness. Treatment principle: Strengthen the spleen and tonify qi. Prescription: Modified Xiangsha Liujunzi Tang. Ingredients: 10 g of Dangshen, 10 g of Baizhu, 10 g of Fuling, 6 g of Zhigancao, 10 g of Banxia, 6 g of Chenpi, 5 g of Muxiang, and 3 g of Sharen. Decoct in water and take one dose daily. If experiencing cold limbs, add Fuzi and Paojiang.
2. Qi and blood deficiency Manifestations: Pale complexion, fatigue, dizziness and palpitations, shortness of breath and reluctance to speak, pale and plump tongue, thin coating, and moist, fine pulse. This type is commonly seen in patients with acute blood loss or severe iron-deficiency anemia. Treatment principle: Tonify both qi and blood. Prescription: Modified Bazhen Tang. Ingredients: 10 g of Dangshen, 10 g of Huangqi, 10 g of Baizhu, 10 g of Danggui, 15 g of Shudi, 6 g of Chenpi, 5 g of Zhigancao, and five dates. Decoct in water and take one dose daily. For those with excessive menstrual bleeding or persistent metrorrhagia, add Ejiao and Aiye Tan to tonify blood and stop bleeding. At the same time, if the patient has severe anemia, increase the dosage of Huangqi to reflect the idea that “visible blood cannot be produced quickly, but invisible qi must be strengthened urgently.” Anemia caused by folate or vitamin B12 deficiency, or by certain drugs that affect nucleotide metabolism and lead to impaired DNA synthesis, is called megaloblastic anemia (MA). This condition is characterized by macrocytic anemia, with the appearance of megaloblasts, granulocytes, and megakaryocytes in the bone marrow. Causes and Pathogenesis