Overview
Aplastic anemia, or aplastic anemia AA, is a group of diseases characterized by hematopoietic failure of bone marrow caused by multiple etiologies (including chemicals, biological factors, radiation, and unknown causes) and characterized by hematopoietic stem cell injury, bone marrow steatosis, and peripheral blood whole blood cell reduction.
The incidence rate in China is 0.74 (0.67-0.82) per 100,000 per year, including 0.14 per 100,000 for acute and 0.6 per 100,000 for chronic reoccurrence.
It is more common in young adults and more common in males.
There are two categories of reoccurrence: congenital and acquired, with acquired reoccurrence accounting for the majority. Acquired reoccurrence is divided into primary and secondary reoccurrence. Primary reoccurrence is much higher than secondary reoccurrence.
The reocclusion belongs to the category of “deficiency labor”, “internal injury and fever” and “blood evidence” in Chinese medicine.
Etiology and pathogenesis
I. Etiology
1. Chemical factors.
(1) When the dose is sufficient, it can cause re-infarction (partly reversible)
Benzene and its derivatives, alkylating agents, antimetabolites, antimitotic agents, antineoplastic agents, inorganic arsenic agents, estrogens, etc.
(2) Related to individual sensitivity
Antibiotics such as chloramphenicol, organic arsenic, sulfonamides, anticonvulsants, antithyroid agents, drugs for diabetes, antihistamines, anti-inflammatory and analgesic drugs, sedatives, antituberculosis drugs, antimalarials, etc.
The most common causes are benzene and its derivatives, chloramphenicol, and anti-inflammatory and analgesic drugs.
2.Physical factors: X-rays, radionuclides, radium, etc., related to the exposure dose.
3.Biological factors: viral infections, such as viral hepatitis, HIV, dengue fever, etc.
Second, the pathogenesis
1. Decrease in hematopoietic stem cells or intrinsic defects (the “seed” theory).
(1) The degree of CD34+ cell reduction correlates with the severity of the disease.
(2) T lymphocytes and their secreted hematopoietic regulatory factors can damage CD34+ cells.
2. Defects in the bone marrow hematopoietic microenvironment (the “land” theory).
Abnormalities of the main bone marrow stromal cells and their secreted hematopoietic factors.
3. Abnormalities of immune mechanism (“worm” theory).
Mainly T4 ↓, T8 ↑, IL-1 ↓, IL-2 ↑, IFN-γ ↑ NK cells ↓.
4, genetic predisposition: susceptibility
Pathology
The main pathological change is the reduction of total red marrow throughout the body, which is replaced by adipose tissue and becomes yellow marrow. Acute reoccurrence mainly affects the earlier pluripotent stem cells, so that they cannot differentiate to the primitive cells, and the red marrow is extensively and severely destroyed, with few various hematopoietic cells in the bone marrow and significantly more non-hematopoietic cells. In chronic remitting disease, the red marrow is only partially destroyed and shows centripetal atrophy and steatosis; the iliac bone is involved first, followed by the sphenoid process and the sternum. The well-proliferating parts show compensatory hyperplasia and focal hyperplasia is active. Lymphatic tissue, such as the spleen, and lymph nodes have varying degrees of atrophy.
Clinical manifestations
The main clinical manifestations of retrolithiasis are progressive anemia, hemorrhage and recurrent infections.
Anemia: generally progressive. It is mainly caused by the failure of bone marrow hematopoietic function.
Hemorrhage: mainly due to reduced platelet production. There are also platelet mass abnormalities and increased capillary permeability.
Infection: due to decreased granulocytes and monocytes and decreased defense function of the body. In addition, it is also associated with decreased gamma globulin and atrophy of lymphoid tissue.
Clinical typing
1. Acute type AA (AAA), also known as heavy remitting type I (SAA-I)
The onset of the disease is rapid, the progression is rapid, and the three major symptoms are obvious and serious.
2.Chronic type AA
The onset and progression are slow and the course of the disease is long. The three major symptoms are mild and easy to control.
Laboratory tests
1.Peripheral blood picture
All three lines are reduced, and the reduction of the three lines is not necessarily parallel, among which the reduction of the absolute value of reticulocytes is the most important.
2.Bone marrow examination
In acute AA, the bone marrow picture is hypoproliferative, and in severe cases, it is depleted.
The bone marrow picture of chronic AA varies in different parts of the body, but megakaryocytopenia is its characteristic.
Diagnosis
The 4th National Academic Conference on Recanalization in 1987
1. complete blood cytopenia with a decrease in the absolute value of Ret.
2, general absence of splenomegaly
3.Bone marrow is at least partially hypoproliferative or severely hypoproliferative (if there is active proliferation, there must be a significant decrease in megakaryocytes), and the bone marrow has an increase in small granular nonhematopoietic cells.
4.Exclude other diseases that cause allogeneic cytopenia, such as MDS, AML, myelofibrosis, malignant group, and especially PNH.
5. General anti-anemia drug therapy is ineffective.
Clinical typing diagnosis
I. Heavy reoccurrence type I.
1, clinical manifestations: rapid onset, progressive increase in anemia, often accompanied by severe infection and visceral bleeding.
2. Hematology: In addition to a rapid decrease in Hb, two of the following must be present
(1) Reticulocytes <1%, absolute value <15×109/L.
(2) Significant decrease in white blood cells, absolute value of neutrophils <0.5×109/L.
(3) Platelets <20×109/L.
3.Bone marrow image
(1) Multi-site hypoplasia, marked decrease in the three lineages of hematopoietic cells, and increase in non-hematopoietic cells. If hyperplasia is active there is lymphocytosis.
(2) The bone marrow has more non-hematopoietic cells and adipocytes in small granules.
Chronic reoccurrence
1. Clinical manifestations: slow onset, less anemia, infection and bleeding.
2. Blood picture: Hb decreases slowly, reticulocytes, leukocytes, neutrophils and platelets are lighter than heavy reoccurrence.
3.Bone marrow image.
(1) The third or second lineage is reduced, and at least one part is poorly proliferated. If the proliferation is good, there is often an increase of late juvenile red in the red lineage, and the megakaryocytes are obviously reduced.
(2) Increased non-hematopoietic cells and adipocytes in bone marrow granules.
4. If the disease deteriorates during the course of the disease, the clinical manifestations, blood and bone marrow images are similar to those of heavy reoccurrence type I. It is called heavy reoccurrence type II.
Foreign diagnostic typing
Heavy reoccurrence.
1.The degree of bone marrow cell hyperplasia is <25% of normal; if it is <50% of normal, the hematopoietic cells should be <30%.
2.Blood picture:with two of the following three items
(1) Granulocytes <0.5×109/L, if <0.2×109/L is very heavy.
(2) Reticulocytes <1% or absolute value <4×109/L.
(3) Platelets <20×109/L.
Differential diagnosis
I. Paroxysmal sleep hemoglobinuria
Hemolytic bone marrow image, clinical manifestations of hemolysis, positive Ham test, positive Rous test
B. Myelodysplastic syndrome
Active myelodysplasia, pathological hematopoiesis of three lines
Malignant histiocytosis
Abnormal histiocytes in bone marrow
Treatment
I. Supportive therapy and symptomatic treatment
II. Androgens: good for chronic retrolithiasis, such as Conradon, testosterone undecanoate, Danazol.
III. Immunosuppressants.
ALG/ATG is mainly used for heavy reoccurrence.
CsA, high-dose methylprednisolone, high-dose gammaglobulin.
Hematopoietic factors: EPO, G-CSF, GM-CSF.
V. Traditional Chinese medicine treatment
In 1982, the first conference on combined traditional Chinese and Western medicine in hematology was held to classify: kidney yin deficiency (Zuo Gui Drink, Da Cuscuta Drink), kidney yang deficiency (Right Gui Wan, Jin Kui Kidney Qi Wan), kidney yin and yang deficiency (Right Gui Drink plus reduction), spleen and kidney yang deficiency (Gui Bai Bai Tang combined with Si Jun Zi Tang), liver and kidney yin deficiency (Liu Wei Di Huang Tang, Da Cuscuta Drink plus reduction).
Principles: “tonifying the kidney is the mainstay, supplemented by tonifying qi”; “tonifying yang is the mainstay, supplemented by nourishing yin”; “first reduce the symptoms, then generate blood” “cool, warm, hot “. The effective drugs screened: ginseng, astragalus, angelica rehmanniae, shouwu, cistanches, bacopa monniera, bone fructus, cuscuta, cynomorium, deer antler, sapodilla, cinnamon, etc.
Sixth, bone marrow transplantation: mainly used for heavy reoccurrence before the age of 40.
VII. Others: splenectomy, embryonic liver infusion
Commonly used androgens, efficacy and side effects in the treatment of chronic reoccurrence
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Dosage and administration Efficacy (%) Side effects
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Protesterone 50-100 ml/d 50.8-80.2 masculinization, water sodium retention
im Cholestatic jaundice
Conlipram 6-12mg/d 59.5-88.9 GPT ↑
divided into 3 times P.O.
Daliapine 30mg/d 86 GPT↑
divided into 3 times P.O.
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VII. Discussion
Overall
1.With the progress of research, the treatment of reoccurrence has achieved better clinical efficacy than before, especially the use of immunosuppressants such as cyclosporine has opened up a new way of treating reoccurrence.
2.The effect of combined Chinese and Western medicine treatment and early treatment is obviously better than simple Chinese medicine or simple Western medicine treatment. Through the combined treatment of Chinese and Western medicines, the efficiency rate is maintained at about 90% after 3 months of treatment.
3.The effect of initial treatment is better than that of patients with relapse or prolonged relapse.
4, when the condition or clinical remission such as symptoms significantly improved, blood cells, especially the number of red blood cells, hemoglobin, platelets and white blood cells and other experimental data close to or back to the normal range, but also to maintain treatment for a period of time, do not stop treatment too early, which may easily lead to relapse. The treatment after relapse will be very difficult.
5, appropriate blood transfusion, before the early treatment has not achieved results, according to the peripheral blood cells, especially red blood cells, hemoglobin and platelets, but can be appropriate transfusion of concentrated red blood cells or platelets, but to strictly limit the transfusion index, on the one hand, to reduce the economic burden, to relieve the pressure of blood supply tension, on the other hand, the subsequent treatment and recovery is also helpful
6. It is not advisable to use ATG excessively and prematurely, especially bone marrow stem cell transplantation, which is a risky and expensive unconventional treatment. There are actually many profound lessons in this regard. The current marketization of medical care has led to a very serious irrational use of expensive drugs, and medical units and individuals are driven by profit to use high-intensity treatments at every turn, overwhelming patients without a corresponding improvement in outcomes. This is a and widespread social phenomenon that must cause individual physicians and medical units to reflect on it. In fact, many treatments, which originated in foreign countries but are severely restricted, are abused in China. With the media’s exaggeration, some treatments that are not mature or definite are abused, which both raise the cost of treatment and add unnecessary financial burden to patients, while increasing the proportion of medical risks and doctor-patient disputes. Both for patients and individual physicians, especially when dealing with a major disease such as aplastic anemia, it is important to consider treatment outcomes and treatment options in the long run. It is beneficial to both society and individuals to consider both patient safety and efficacy, as well as economic costs.