| disease | Aplastic Anemia |
| alias | Re-disability, Aplastic Anemia |
Aplastic anemia (AA) is a syndrome caused by various disease factors leading to hematopoietic dysfunction, characterized by a reduction in total red bone marrow volume, replacement with fatty marrow, hematopoietic failure, and pancytopenia as the main manifestation. According to a survey conducted in 21 provinces (municipalities) and autonomous regions in China, the annual incidence rate is 0.74 per 100,000 population, significantly lower than that of leukemia. The incidence of chronic aplastic anemia is 0.60 per 100,000 population, while acute aplastic anemia is 0.14 per 100,000 population. It can occur in all age groups but is more common in young adults, with a slightly higher incidence in males than in females.
bubble_chart Etiology
The onset of aplastic anemia may be related to the following factors:
(1) Drugs Drugs are the most common cause of the disease. Drug-induced aplastic anemia can be classified into two types: ① Dose-dependent, which is due to the toxic effects of the drug. When a certain dose is reached, it can cause bone marrow suppression, which is generally reversible, such as various anti-tumor drugs. Cell cycle-specific drugs like cytarabine and methotrexate primarily target more mature pluripotent stem cells that are prone to division. Therefore, when pancytopenia occurs, the bone marrow still retains a certain number of pluripotent stem cells, and the aplastic anemia can recover after discontinuation of the drug. Drugs like busulfan and nitrosoureas not only affect stem cells in the proliferative cycle but also target non-proliferative stem cells, often leading to prolonged bone marrow suppression that is difficult to reverse. Additionally, drugs such as phenytoin sodium, phenothiazines, thiouracil, and chloramphenicol can also cause dose-dependent bone marrow suppression. ② Dose-independent, where only a few patients experience hematopoietic dysfunction, often due to drug hypersensitivity reactions, which can lead to persistent aplastic anemia. There are many types of drugs in this category, including chloramphenicol, organic arsenic, quinacrine, trimethadione, phenylbutazone, gold preparations, aminopyrine, piroxicam, sulfonamides, thiamphenicol, carbimazole, methimazole, and chlorpropamide, among others. The most common drug-induced aplastic anemia is caused by chloramphenicol. According to domestic surveys, the risk of developing aplastic anemia within six months of taking chloramphenicol is 33 times higher than in the control group, with a dose-response relationship. Chloramphenicol can cause both types of drug-induced aplastic anemia. The chemical structure of chloramphenicol contains a nitrobenzene ring, and its bone marrow toxicity is related to nitrosyl-chloramphenicol, which can inhibit mitochondrial DNA polymerase in bone marrow cells, leading to reduced DNA and protein synthesis, as well as inhibit heme synthesis. Vacuoles may appear in the cytoplasm of erythroblasts, and sideroblasts may increase. This suppression is reversible, and blood counts recover once the drug is discontinued. Chloramphenicol can also cause dose-independent hypersensitivity reactions, leading to bone marrow suppression, which may occur weeks or months after taking the drug or suddenly during treatment. The mechanism may involve direct suppression of hematopoietic stem cells or chromosomal damage through autoimmune reactions. This type of effect is often irreversible, even after discontinuing the drug. Individuals with hereditary defects in stem cells are more sensitive to chloramphenicol.
(2) Chemical Toxins The relationship between benzene and its derivatives and aplastic anemia has been confirmed by numerous experimental studies. Benzene tends to accumulate in fat-rich tissues in the human body, and in chronic benzene poisoning, it primarily accumulates in the bone marrow. The bone marrow toxicity of benzene is caused by its metabolites, which can act on hematopoietic progenitor cells, inhibit DNA and RNA synthesis, and damage chromosomes. Since the reform and opening up, the rise of township enterprises, coupled with inadequate labor protection, has led to an increase in the incidence of benzene poisoning-induced aplastic anemia. Benzene poisoning-induced aplastic anemia can manifest as a chronic type or an acute severe type, with the latter being more common.(3) Ionizing Radiation X-rays, gamma rays, or neutrons can penetrate or enter cells, directly damaging hematopoietic stem cells and the bone marrow microenvironment. Long-term exposure to radiation doses exceeding permissible limits (e.g., radiation source accidents) can lead to aplastic anemia.
(4) Viral Infection The relationship between viral hepatitis and aplastic anemia (AA) is well-established, referred to as hepatitis-associated aplastic anemia (HAAA), which is one of the most severe complications of viral hepatitis. Its incidence is less than 1.0%, accounting for 3.2% of AA patients. The specific type of hepatitis causing AA remains uncertain, with approximately 80% attributed to non-A, non-B hepatitis (likely hepatitis C) and the rest to hepatitis B. Clinically, HAAA presents in two forms: - The **acute type** is more common, characterized by rapid onset. The average interval between hepatitis and AA onset is about 10 weeks. By the time AA develops, hepatitis is usually in the **stage of convalescence**, but AA is severe, with a short survival period. This form predominantly occurs in younger patients, mostly following non-A, non-B hepatitis. - The **chronic type** is rarer, often developing on the basis of chronic hepatitis B. It is milder, with a longer interval between hepatitis and AA onset, and a longer survival period. The **mechanism of disease** remains unclear. The hepatitis virus may directly suppress hematopoietic stem cells, induce chromosomal aberrations, or trigger virus-mediated autoimmune abnormalities. Viral infection can also disrupt the bone marrow microcirculation.
(6) Genetic factors Fanconi anemia is an autosomal recessive genetic disorder with familial occurrence. Anemia typically manifests between 5 to 10 years of age, and most cases are accompanied by congenital malformations, particularly in the skeletal system, such as short or absent thumbs, polydactyly, shortened radius, short stature, microcephaly, narrow eye fissures, strabismus, deafness, renal malformations, and cardiovascular malformations. Skin pigmentation is also common. This disease is often associated with elevated HBF, a high incidence of chromosomal abnormalities, and defective DNA repair mechanisms, leading to a significantly increased risk of malignancies, especially leukemia. About 10% of affected children have parents with a history of consanguineous marriage.
(7) Paroxysmal nocturnal hemoglobinuria (PNH) PNH and aplastic anemia are closely related. About 20–30% of PNH cases may be accompanied by aplastic anemia, while 15% of aplastic anemia cases may develop overt PNH. Both are diseases of hematopoietic stem cells. Clear progression from aplastic anemia to PNH, where aplastic anemia symptoms are no longer evident; or clear progression from PNH to aplastic anemia, where PNH symptoms are no longer evident; or cases of PNH with aplastic anemia or aplastic anemia with PNH red blood cells—all may be referred to as aplastic anemia-PNH syndrome.
(1) Reduction or Defects in Hematopoietic Stem Cells A large number of experimental studies have confirmed that hematopoietic stem cell deficiency or defects are the primary pathophysiological mechanism of aplastic anemia. At least half of the cases of aplastic anemia are caused by hematopoietic stem cell deficiency. In vitro culture of bone marrow progenitor cells from patients shows significant reductions in CFU-GM, BFU-E, CFU-E, and CFU-GEMM measurements, along with an increased ratio of cell clusters/colonies formed by CFU-C. The rapid restoration of normal hematopoietic function following successful syngeneic bone marrow transplantation further supports that the primary mechanism of aplastic anemia is hematopoietic stem cell deficiency or defects. For example, when animals are first subjected to busulfan-induced stem cell injury and then treated with chloramphenicol, further reductions in CFU-S and CFU-C occur, leading to aplastic anemia. This suggests that stem cell defects likely precede the development of aplastic anemia under the influence of various environmental factors.
(2) Defects in the Hematopoietic Microenvironment The concept of the hematopoietic microenvironment includes both the structural components of hematopoietic tissue that support hematopoiesis and the regulatory factors involved. Hematopoietic cells proliferate and differentiate within the reticular scaffold formed by stromal cells. The stromal cell population includes fibroblasts, reticular cells, macrophages, and others, which can form CFU-F in vitro cultures. Hematopoietic stem cells can only proliferate when surrounded by stromal cells. In some aplastic anemia patients, bone marrow cultures fail to form CFU-F, while CFU-GM remains normal, indicating that the disease mechanism in these patients is due to microenvironmental defects. Hematopoietic regulatory factors include numerous humoral factors and intercellular interactions. Some aplastic anemia patients exhibit abnormalities in humoral and cellular regulatory mechanisms of hematopoietic stem cells, such as increased inhibitory T cells, decreased helper T cells, reduced natural killer cell activity, elevated levels of negative hematopoietic regulators like interferon-γ, tumor necrosis factor, and interleukin-2, as well as decreased cAMP levels. These factors may contribute to the disordered proliferation and differentiation of hematopoietic stem cells in aplastic anemia.
(3) Immune Suppression of Hematopoietic Stem Cells In aplastic anemia secondary to systemic lupus erythematosus and rheumatoid arthritis, autoantibodies against hematopoietic stem cells are present in the serum. In some cases of primary aplastic anemia, T lymphocytes can inhibit the growth of normal hematopoietic progenitor cells, and the removal of T lymphocytes restores normal growth of granulocytic and erythroid colonies. In some patients, although bone marrow transplantation is unsuccessful, the administration of high-dose immunosuppressants leads to the recovery of their own hematopoietic function. All these observations indicate that inhibitory T lymphocytes play a role in the pathophysiology of some cases of aplastic anemia.
bubble_chart Pathological Changes
(1) Bone marrow lesions in aplastic anemia The main pathological change is the reduction of hematopoietic tissue, with a decrease in the total volume of red marrow replaced by adipose tissue. In normal adults, the ratio of hematopoietic tissue to adipose tissue in the bone marrow is approximately 1:1, whereas in aplastic anemia, it often exceeds 2:3. In hematopoietic foci, hematopoietic cells (referring to the granulocytic, erythroid, and megakaryocytic systems) are reduced, while "non-hematopoietic cells" (referring to lymphocytes, plasma cells, tissue basophils, and reticular cells) increase. The bone marrow exhibits plasma exudation, hemorrhage, lymphocyte proliferation, focal fibrosis, and interstitial lesions. In acute aplastic anemia, bone marrow lesions develop rapidly and extensively; in chronic cases, they progress gradually as "centripetal atrophy," first affecting the iliac bone, followed by the spinous processes and sternum. Chronic aplastic anemia also presents compensatory hyperplastic foci, primarily characterized by erythroid hyperplasia with maturation disorders. Erythroid cells not only decrease in number but also exhibit qualitative defects. Ultrastructural observations reveal abnormal mature erythrocytes with petal-like shapes, myeloid changes in the cytoplasm of erythroblasts, imbalanced nuclear-cytoplasmic development, and enlarged nuclear membrane pores. Additionally, erythrocytes show increased alkali-resistant hemoglobin and free protoporphyrin, as well as reduced activity of erythrocyte enzymes such as pyruvate kinase. These findings collectively indicate qualitative abnormalities in erythrocytes. Iron kinetic studies demonstrate elevated plasma iron, increased sideroblasts and tissue iron, delayed plasma iron clearance, and significantly reduced iron uptake by erythrocytes, suggesting a decreased erythrocyte production rate. Some patients also exhibit ineffective erythropoiesis or intramedullary hemolysis.
(2) Lesions in organs outside the bone marrow Autopsy findings reveal hemorrhages in the skin and mucous membranes, as well as visceral hemorrhages, most commonly in the heart, gastrointestinal tract, and lungs. The incidence of cerebral hemorrhage is 52.6%. The primary causes of hemorrhage are thrombocytopenia and vascular wall abnormalities, the latter manifesting as morphological and functional changes in nailfold capillaries. Platelets also exhibit qualitative abnormalities, with small platelets accounting for 50%, displaying irregular shapes, fewer projections, transparent cytoplasm, and reduced granules. Platelet adhesion, aggregation, and factor III activity are significantly lower than normal. Heparin-like substances appear in the blood, along with increased protein C antigen levels and elevated antithrombin III activity. Patients with aplastic anemia are prone to various infections, predominantly caused by Gram-negative bacilli, including *Escherichia coli*, *Pseudomonas aeruginosa*, and *Staphylococcus aureus*. Besides the skin and mucous membranes, the gastrointestinal tract—due to impaired barrier function, hemorrhage, or mucosal ulcers—is also a significant entry site for pathogens. The decline in the body's defense mechanisms, reductions in granulocytes and monocytes, and atrophy of lymphoid tissue are closely related, with the latter being particularly pronounced in acute aplastic anemia, leading to varying degrees of cellular and humoral immune abnormalities. Repeated blood transfusions may result in hemosiderin deposition and even secondary hemochromatosis. The primary causes of death in this condition are intracranial hemorrhage, heart failure, pulmonary edema, and severe infections.
bubble_chart Clinical Manifestations
It is divided into two major categories: congenital and acquired, with the acquired type accounting for the vast majority. Congenital aplastic anemia is extremely rare, with Fanconi anemia being its primary type. Acquired aplastic anemia can be further classified into primary and secondary types. The former refers to cases of unknown cause, accounting for approximately 50% of acquired aplastic anemia. It can also be comprehensively classified into acute and chronic types based on clinical manifestations, blood tests, and bone marrow findings. Internationally, severe aplastic anemia is categorized as grade III, with the diagnostic criteria requiring two of the following three blood test abnormalities: ① Absolute neutrophil count <500/mm3, ② Platelet count <20,000/mm3, ③ Corrected reticulocyte count (hematocrit-adjusted) <1%; bone marrow cellularity must be less than 25% of normal, or if less than 50%, hematopoietic cells must be less than 30%. Cases with an absolute neutrophil count <200/mm3 are termed very severe aplastic anemia. At the Fourth National Conference on Aplastic Anemia in 1987, acute aplastic anemia was designated as severe aplastic anemia type I, while chronic aplastic anemia that transforms into an acute phase [third stage] was termed severe aplastic anemia type II.
(1) Acute Aplastic Anemia: The onset is abrupt, with rapid progression, often presenting initially and primarily with bleeding and infection (fever). Anemia may not be obvious at the onset but becomes progressively worse as the disease advances. Bleeding tendencies are almost universal, with over 60% of cases involving visceral bleeding, primarily manifesting as gastrointestinal bleeding, hematuria, retinal hemorrhage (often accompanied by visual impairment), and intracranial hemorrhage. Skin and mucosal bleeding is widespread and severe, often difficult to control. Fever due to infection is almost always present during the course of the disease, frequently leading to necrotic ulcers in the oropharynx and perianal regions, which can result in sepsis. Pneumonia is also common. Infection and bleeding exacerbate each other, worsening the condition. Without aggressive treatment, most patients die within a year.
(2) Chronic Aplastic Anemia: The onset is gradual, with anemia being the initial and primary manifestation. Bleeding is usually limited to the skin and mucous membranes and is not severe. Infections may occur but are typically respiratory in nature and easier to control. With appropriate and persistent treatment, many patients can achieve long-term remission or even complete recovery. However, some cases may persist for many years without improvement, with disease courses lasting even decades. A minority of patients may develop acute aplastic anemia-like clinical manifestations in the late stage [third stage], referred to as chronic aplastic anemia with acute transformation.
bubble_chart Auxiliary Examination
(1) Blood Picture The condition manifests as pancytopenia. The anemia is normocytic, but may also present as grade I macrocytic. Red blood cells exhibit grade I anisocytosis without significant poikilocytosis or polychromasia, and nucleated red blood cells are generally absent. Reticulocytes are markedly reduced.
(2) Bone Marrow Picture In the acute form, hypoplasia or grade III hypoplasia is observed in multiple sites, with a significant reduction in all three hematopoietic cell lines, particularly megakaryocytes and nucleated red blood cells. Non-hematopoietic cells are increased, especially lymphocytes. In the chronic form, bone marrow findings vary widely depending on the puncture site, ranging from hypoplasia to hyperplasia, but at least one site must show hypoplasia. If hyperplasia is present, the proportion of late erythroblasts (pyknotic nuclei) is often increased, with irregularly lobulated nuclei and impaired enucleation, while megakaryocytes are markedly reduced. Macroscopically, bone marrow smears show increased fat droplets, and microscopic examination of marrow particles reveals an increase in non-hematopoietic cells and adipocytes, typically exceeding 60%.
(3) Bone Marrow Biopsy and Radionuclide Bone Marrow Scanning Since bone marrow smears are susceptible to dilution by peripheral blood, one or two smears may not accurately reflect hematopoietic status. Bone marrow biopsy provides a better assessment of cellularity than smears and improves diagnostic accuracy. Whole-body γ-imaging with technetium-99m sulfur colloid or indium-111 chloride reflects the distribution of functional bone marrow. In aplastic anemia, radioactive uptake is reduced or absent in normal marrow sites, indirectly indicating the extent and location of hematopoietic tissue depletion.
(4) Other Tests Hematopoietic progenitor cell culture not only aids in diagnosis but also helps detect inhibitory lymphocytes or serum inhibitory factors. Alkaline phosphatase activity in mature neutrophils is elevated, while serum lysozyme activity is reduced. Fetal hemoglobin levels are increased. Chromosomal analysis is typically normal in aplastic anemia, except for Fanconi anemia, which shows frequent aberrations. If karyotypic abnormalities are present, myelodysplastic syndrome must be excluded.
The diagnostic criteria for aplastic anemia revised at the Fourth National Aplastic Anemia Academic Conference in 1987 are as follows: ① Pancytopenia with a reduced absolute reticulocyte count. ② Generally no splenomegaly. ③ Bone marrow examination shows hypoplasia or grade III hypoplasia in at least one site (if hyperplasia is present, megakaryocytes should be significantly reduced, and non-hematopoietic cells should be increased in bone marrow particles. Bone marrow biopsy and other tests should be performed when possible). ④ Other diseases that cause pancytopenia must be excluded, such as paroxysmal nocturnal hemoglobinuria, refractory anemia in myelodysplastic syndrome, acute hematopoietic arrest, myelofibrosis, acute leukemia, malignant histiocytosis, etc. ⑤ Generally ineffective with conventional anti-anemia treatment.
bubble_chart Treatment Measures
Including disease cause treatment, supportive therapy, and various measures to promote the recovery of bone marrow hematopoietic function. For chronic cases, androgens are generally the mainstay, supplemented by other comprehensive treatments. Satisfactory results can only be achieved through long-term and persistent efforts. In many cases, hemoglobin levels return to normal, but platelets remain at relatively low levels for an extended period. If there are no clinical signs of bleeding, patients can resume light work. Acute cases have a poor prognosis, and the aforementioned treatments are often ineffective. Once diagnosed, early selection of bone marrow transplantation or anti-lymphocyte globulin therapy is advisable.
(1) Supportive therapy: All substances that may cause bone marrow damage should be removed, and any drugs that inhibit bone marrow function are strictly prohibited. Active personal hygiene and nursing care are essential. For patients with granulocytopenia, protective isolation and proactive infection prevention are recommended. Blood transfusions should be administered based on strict indications. For those preparing for bone marrow transplantation, transfusions before the procedure can directly affect the success rate, especially transfusions from family members. Generally, concentrated red blood cells are preferred. For severe bleeding, concentrated platelets should be transfused, and single-donor or HLA-matched platelet transfusions can improve efficacy. Patients requiring repeated transfusions should undergo deferoxamine therapy for iron removal.
(2) Androgens: These are the first-line drugs for treating chronic aplastic anemia. Commonly used androgens fall into four categories: ① 17α-alkyl androgens, such as stanozolol (Stanozolone), methandrostenolone, oxymetholone, fluoxymetholone, and Dianabol; ② Testosterone esters, such as testosterone propionate, testosterone enanthate, testosterone cypionate, testosterone undecanoate (Andriol), and mixed testosterone esters (testosterone propionate, testosterone valerate, and testosterone undecanoate), also known as "Triolandren"; ③ Non-17α-alkyl androgens, such as nandrolone phenylpropionate and nandrolone decanoate; ④ Intermediate active metabolites, such as etiocholanolone and danazol. Testosterone, once ingested, is converted into the more potent 5α-dihydrotestosterone by 5α-reductase in kidney tissues and macrophages, stimulating the kidneys to produce erythropoietin and macrophages to produce granulocyte-macrophage colony-stimulating factor. In the liver and renal medulla, 5β-reductase degrades testosterone into 5β-dihydrotestosterone and etiocholanolone, both of which directly stimulate hematopoietic stem cells, promoting their proliferation and differentiation.
Therefore, androgens can only be effective when a certain amount of residual hematopoietic stem cells is present. They are often ineffective for acute and severe aplastic anemia. For chronic cases, they show some efficacy, but high doses and prolonged use are required. Testosterone propionate is administered intramuscularly at 50–100 mg/day, stanozolol orally at 6–12 mg/day, testosterone undecanoate orally at 120–160 mg/day, and Triolandren intramuscularly at 250 mg twice weekly. The treatment course should last at least six months.
Domestic reports indicate an efficacy rate of 34.9–81% and a remission rate of 19–54%. Erythroid response is generally better, with reticulocytes rising after one month, followed by hemoglobin levels. White blood cell counts begin to rise after two months, but platelet recovery is often difficult. Some patients develop androgen dependence, with a relapse rate of 25–50% after discontinuation. Re-treatment can still be effective. Testosterone propionate has significant masculinizing side effects, including acne, hirsutism, voice deepening, amenorrhea in women, accelerated bone maturation in children, and early epiphyseal fusion, along with some degree of water and sodium retention. Repeated intramuscular injections of testosterone propionate often cause local indurations, so rotating injection sites is recommended. 17α-alkyl androgens have milder masculinizing side effects than testosterone propionate but significantly higher hepatotoxicity. Most patients experience elevated alanine aminotransferase levels, and severe cases may develop intrahepatic cholestatic jaundice. A few may even develop hepatic hemangiomas or hepatocellular carcinoma, but these conditions usually resolve after discontinuation.
(3) Bone marrow transplantation is the best method for treating aplastic anemia caused by stem cell defects and can achieve the goal of radical cure. Once severe or very severe aplastic anemia is diagnosed, if the patient is under 20 years old and has an HLA-matched donor, allogeneic bone marrow transplantation should be the first choice in qualified hospitals. The long-term disease-free survival rate after transplantation can reach 60–80%. However, transplantation should be performed as early as possible, as initial patients often receive red blood cell and platelet transfusions, which can easily sensitize the recipient to minor histocompatibility antigens of the blood donor, leading to an increased incidence of transplant rejection. For patients who have not received blood transfusions or have had very few transfusions after diagnosis, the pretreatment regimen can use cyclophosphamide at 50 mg/kg per day, administered by continuous intravenous infusion for 4 days.
Allogeneic bone marrow transplantation has been applied domestically to treat severe aplastic anemia, with successful cases reported. Those who undergo successful transplantation can expect a cure. Fetal liver cell suspension infusion therapy for aplastic anemia has been widely adopted in China, with some believing it can promote or assist in the recovery of hematopoietic function. However, its exact efficacy and mechanism require further research.
(IV) Immunosuppressants Suitable for severe aplastic anemia in patients over 40 years old or those without suitable bone marrow donors. The most commonly used agents are antithymocyte globulin (ATG) and antilymphocyte globulin (ALG). The mechanism may primarily involve eliminating the inhibitory effect of suppressor T lymphocytes on bone marrow hematopoiesis. Some also suggest an immunostimulatory effect, promoting stem cell proliferation by increasing hematopoietic regulatory factors. Additionally, there may be a direct stimulatory effect on hematopoietic stem cells themselves. **Dosage** varies depending on the source: - Horse ALG: 10–15 mg/(kg·d) - Rabbit ATG: 2.5–4.0 mg/(kg·d) Administered over 5 days, diluted in normal saline. A skin test is performed first, followed by slow intravenous infusion through a large vein. If no reaction occurs, the full dose is infused over 8–12 hours. Concurrently, hydrocortisone is administered intravenously—half the dose before ALG/ATG infusion and the other half after. Patients should ideally be placed in protective isolation. To prevent serum sickness, oral prednisone at 1 mg/(kg·d) is recommended starting on day 5, halved after day 15, and discontinued by day 30. High-dose corticosteroids should be avoided to prevent femoral head avascular necrosis. Therapeutic effects typically appear after 1 month, sometimes after 3 months. The response rate for severe aplastic anemia is 40–70%, with 50% of responders achieving long-term survival. **Adverse reactions** include fever, chills, rash (allergic reactions), infections and bleeding due to neutropenia and thrombocytopenia, infusion-site phlebitis, and serum sickness occurring 7–10 days post-treatment. Cyclosporine A (CSA) is another common drug for severe aplastic anemia, preferred over ALG/ATG due to its convenience and safety. Its mechanism may involve selective action on T lymphocyte subsets, inhibiting the activation and proliferation of suppressor T cells, and suppressing the production of IL-2 and gamma interferon. **Dosage**: 10–12 mg/(kg·d), with most cases requiring long-term maintenance therapy at 2–5 mg/(kg·d). The response rate is also 50–60%, with effects appearing after 1–2 months. **Adverse reactions** include hepatotoxicity, nephrotoxicity, hypertrichosis, gingival hyperplasia, and muscle tremors. Blood concentration monitoring is recommended for safe use, with an effective range of 300–500 ng/ml. Modern immunosuppressive therapy for severe aplastic anemia yields efficacy comparable to bone marrow transplantation. However, it is not curative and may lead to long-term complications, such as clonal diseases including MDS, PNH, and leukemia.
(V) Traditional Chinese Medicine (TCM) Treatment should focus on **tonifying the kidneys** while also **replenishing qi and invigorating blood**. Commonly used Chinese medicinals include: - Cervi Deer-Horn Glue - Common Curculigo Rhizome - Epimedium Herb - Astragalus Root - Prepared Rehmannia Root - Polygonum Multiflorum - Chinese Angelica - Cistanche - Morinda Root - Psoralea - Dodder Seed - Barbary Wolfberry Fruit - Donkey-hide Gelatin In China, chronic aplastic anemia is often treated with a combination of androgens and TCM kidney-tonifying therapy.
(VI) Hematopoietic Cytokines and Combination Therapy Aplastic anemia is an anemia caused by hematopoietic stem cell disease, with endogenous plasma EPO levels consistently above 500 u/L. Treatment with recombinant human EPO for aplastic anemia requires high doses to be effective, as standard doses typically yield no results. Recombinant colony-stimulating factors, including G-CSF, GM-CSF, or IL-3, may have some effect in increasing neutrophils and reducing infections in aplastic anemia patients, but they show poor efficacy in improving anemia and thrombocytopenia unless administered in high doses. However, hematopoietic cytokines are expensive, so their current use is limited to adjunctive therapy during immunosuppressive treatment for severe aplastic anemia. For example, when ALG/ATG is used to treat severe aplastic anemia, severe neutropenia often leads to infections and early mortality. Concurrent use of rHG-CSF during this period can improve early neutropenia and reduce mortality rates. Combination therapy can enhance treatment efficacy for severe aplastic anemia, including regimens such as ALG/ATG combined with CSA, or CSA combined with androgens. The European Blood and Marrow Transplantation Group has adopted a combination therapy of ALG, CSA, methylprednisolone, and rhG-CSF, achieving an efficacy rate of up to 82% for severe aplastic anemia.
1. Drugs that are harmful to the hematopoietic system should be strictly indicated to prevent abuse. Blood tests should be regularly monitored during use.
2. For workers exposed to hematopoietic system toxins or radioactive materials, various protective measures should be strengthened, and regular blood tests should be conducted.
3. Vigorous efforts should be made to prevent and treat viral hepatitis and other viral infections.
Aplastic anemia must be differentiated from the following diseases:
(1) Paroxysmal nocturnal hemoglobinuria (PNH) Especially in cases without hemoglobinuria, PNH is easily misdiagnosed as aplastic anemia. This condition is less frequently associated with bleeding or infections. Features such as elevated reticulocyte count, erythroid hyperplasia in the bone marrow, positive urine hemosiderin, positive sugar-water test and Ham test, and reduced alkaline phosphatase activity in mature neutrophils can aid in differentiation.
(2) Myelodysplastic syndrome (MDS) The FAB cooperative group classifies MDS into five subtypes, among which refractory anemia can easily be confused with atypical aplastic anemia. Although MDS also presents with pancytopenia, all three hematopoietic cell lineages in the bone marrow show hyperplasia, including megakaryocytes. Dysplastic hematopoiesis is observable in all three lineages. Chromosomal abnormalities are found in 20–60% of cases, and bone marrow biopsy may reveal "abnormal distribution of hematopoietic precursor cells."
(3) Hypoplastic acute leukemia This condition is more common in the elderly, with a slow or rapidly progressive course. The liver, spleen, and lymph nodes are generally not enlarged. Peripheral blood shows pancytopenia, with few or occasional blasts. Although the bone marrow exhibits focal hypoplasia, the percentage of blasts meets the diagnostic criteria for leukemia.
(4) Pure red cell aplasia Aplastic crisis in hemolytic anemia and acute hematopoietic arrest may present with pancytopenia, acute onset, and identifiable triggers. Symptoms may resolve spontaneously after the trigger is removed. Giant proerythroblasts may appear in the bone marrow. Chronic acquired pure red cell aplasia with grade I leukopenia and thrombocytopenia requires differentiation from chronic aplastic anemia.
