II. Clinical Manifestations

The causes of megaloblastic anemia can be divided into: (1) Insufficient dietary nutrition: inadequate intake of folate or vitamin B12; (2) Malabsorption: gastrointestinal diseases, drug interference, and the formation of intrinsic factor antibodies (pernicious anemia); (3) Metabolic abnormalities: liver disease, certain anti-tumor drugs; (4) Increased demand: lactation period, pregnancy; (5) Impaired utilization: abnormal purine and pyrimidine synthesis, or the effects of chemotherapy drugs, etc. Depending on the specific nutrient lacking, the disease can be classified as simple folate-deficiency anemia, simple vitamin B12-deficiency anemia, or combined folate and vitamin B12-deficiency anemia. II. Clinical Manifestations (1) Hematological manifestations: Onset is gradual, often accompanied by pallor, fatigue, decreased endurance, dizziness, palpitations, and other anemic symptoms. In severe cases, there is pancytopenia, recurrent infections, and bleeding. A small number of patients may experience mild jaundice. (2) Gastrointestinal manifestations: Atrophy of the oral mucosa and lingual papillae, with the tongue surface resembling “beef-like tongue,” sometimes accompanied by tongue pain. Atrophy of the gastrointestinal mucosa can lead to loss of appetite, nausea, bloating, diarrhea, or constipation. (3) Neurological manifestations and psychiatric symptoms: Symmetrical distal limb numbness and deep sensory disturbances; ataxia or unsteady gait; diminished taste and smell; positive pyramidal tract signs, increased muscle tone, and hyperreflexia; decreased vision and dark adaptation; in severe cases, urinary and fecal incontinence may occur. Individuals with folate deficiency may exhibit irritability and delusions, while those with vitamin B12 deficiency may experience depression, insomnia, memory decline, hallucinations, delusions, and even mental confusion and personality disorders. III. Laboratory Examinations (1) Hematological findings: Macrocytic anemia, with increased average red cell volume and red cell hemoglobin content, though the average red cell hemoglobin concentration remains normal. Reticulocyte count may be normal or slightly elevated, but in severe cases, pancytopenia occurs. Blood smears may show red cells of varying sizes, with the central pale area disappearing, along with large oval red cells and dotted red cells; neutrophils may have excessively lobed nuclei, and giant rod-shaped nuclei may also appear. (2) Bone marrow examination: Active or markedly active proliferation. Erythroid hyperplasia is prominent, with megaloblastic changes (large cell bodies, relatively mature cytoplasm compared to the nucleus—“mature nucleus, immature cytoplasm”); granulocytic lineage also shows megaloblastic changes, with mature granulocytes having multiple lobes; megakaryocyte volume increases, with excessive lobulation. Bone marrow iron staining is often increased. (3) Measurement of serum vitamin B12, folate, and red cell folate levels: Low serum vitamin B12 and/or folate levels. IV. Diagnosis and Differential Diagnosis () Diagnosis (1) Presence of folate and vitamin B12 deficiency, along with corresponding clinical manifestations; (2) Peripheral blood shows macrocytic anemia, with excessively lobed neutrophil nuclei; (3) Bone marrow exhibits typical megaloblastic changes, with no other pathological hematopoietic manifestations; (4) Serum folate and/or vitamin B12 levels are reduced; (5) Effective trial treatment: If reticulocyte counts rise after about a week of folate or vitamin B12 treatment, consider folate or vitamin B12 deficiency. (II) Differential Diagnosis (1) Hematopoietic system neoplastic diseases: Such as acute myeloid leukemia subtype M6, myelodysplastic syndrome, where the bone marrow shows megaloblastic changes and other pathological hematopoietic phenomena, yet folate and vitamin B12 levels are not low and supplementation is ineffective. (2) Diseases with autoantibodies against red blood cells: Such as autoimmune hemolytic anemia, Evans syndrome, and immune-related pancytopenia. The distinguishing feature is that these patients have characteristics of autoimmune diseases, and immunosuppressive agents are needed to significantly correct the anemia. (3) Anemia associated with high-viscosity blood: Such as multiple myeloma, where M-protein components adhere to red blood cells, making them appear coin-shaped (“string-like”), and automated blood cell counters measure a larger average red cell volume. However, the unique manifestation of myeloma is something MA does not have. (4) Non-hematopoietic system diseases: Such as hypothyroidism and sequelae of tumor chemotherapy. V. Treatment (---) Treatment of the primary disease For MA caused by underlying diseases (such as gastrointestinal diseases, autoimmune diseases, etc.), actively treat the primary disease; for MA secondary to medication, discontinue the drug as appropriate. (II) Supplementing deficient nutrients (1) Folate deficiency: Take oral folate until anemic symptoms completely disappear; if there is no primary disease, maintenance treatment is not necessary; if there is also vitamin B12 deficiency, administer vitamin B12 injections simultaneously, otherwise neurological damage may worsen. (2) Vitamin B12 deficiency: Administer vitamin B12 via intramuscular injection; those without vitamin B12 absorption barriers may take vitamin B12 tablets orally until hematological parameters return to normal; if neurological symptoms appear, maintain treatment for half a year to a year; for patients with pernicious anemia, treatment should be lifelong. VI. Professor Pei Zhengxue’s Experience in Diagnosing and Treating Megaloblastic Anemia (---) Professor Pei Zhengxue’s Understanding of This Disease This disease falls under categories such as “Xulao,” “Chongbing,” and “Weihuang” in traditional Chinese medicine. (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. This disease is caused by impaired spleen and stomach function. According to the “Four Major Treatments for Wind, Labor, and Diaphragm Disorders,” the spleen and stomach are the major source of qi and blood production, as well as the foundation of postnatal life. Specifically, the spleen’s function of transforming food and water into vital energy plays a crucial role in the body’s nutrient absorption and the formation of blood components. The spleen is responsible for transformation and ascending movement, favoring dryness and disliking dampness; the stomach is responsible for receiving and descending, favoring moisture and disliking dryness. Under normal physiological conditions, the spleen and stomach work together—one ascending, one descending; one dry, one moist—to maintain balance in the body’s digestion and absorption functions. Therefore, when the spleen and stomach function is disrupted, and there is no source of qi and blood production, nutritional megaloblastic anemia is easily generated. (III) Professor Pei Zhengxue’s Clinical Experience in Treating This Disease When treating megaloblastic anemia, the first step is to tonify the spleen and stomach, which also combines syndrome differentiation with disease identification. There are two representative prescriptions: one is Xiangsha Liujunzi Tang, and the other is Banxia Xiexin Tang. The former focuses on strengthening the spleen and eliminating dampness, treating symptoms such as fullness, poor appetite, fatigue, vomiting and diarrhea, pale tongue with thin white coating, and deep, fine pulse—similar to chronic gastritis in modern medicine. The latter focuses on harmonizing the stomach and reversing upward flow, suitable for cases of mid-abdominal fullness and discomfort caused by disharmony between cold and heat, or for symptoms such as vomiting or diarrhea, yellow tongue with greasy coating, and rapid, tense pulse—similar to gastritis of the gastric antrum or body, where chronic inflammatory lesions exist in both the antrum and body. During clinical practice, flexible application is required; if dry mouth and little coating appear, add Beishashen, Mai Dong, Yu Zhu, and Shi Hu. For nasal and dental issues, add Dan Pi Tan, Xue Yu Tan, Bo He Tan, and Zong Lu Tan. For diarrhea, add Gan Jiang and Fu Zi; for constipation, add Da Huang and Huang Lian. For low platelet count, add Yu Zhu, Huang Jing, Sheng Di, and Ban Lan Gen.

1. Spleen dampness stagnation 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. Spleen and stomach disharmony Manifestations: Mid-abdominal fullness and discomfort caused by disharmony between cold and heat, or vomiting and diarrhea, yellow tongue with greasy coating, and rapid, tense pulse—similar to chronic gastritis of the gastric antrum or entire stomach, where chronic inflammatory lesions exist in both the antrum and body. Treatment principle: Strengthen the spleen and harmonize the stomach, reverse upward flow.

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Medicinal formula: It is advisable to choose Banxia Xiexin Tang with modifications. Banxia 6g, Huanglian 6g, Ganjiang 6g, Renshen 6g, and Dazao 4 pieces. Decoct in water and take one dose daily.