Leukopenia is a group of syndromes due to a variety of causes. When the peripheral blood leukocyte count in adults is <4.0×109/L, it is called leukopenia; when the absolute peripheral blood neutrophil count is <1.5×109/L, it is called granulocytopenia; when the granulocyte count is <0.5×109/L, it is called granulocyte deficiency.
I. Etiology and pathogenesis
The pathogenesis of leukopenia includes disorders of granulocytogenesis (reduced production of granulocytes in the bone marrow or impaired differentiation and development), excessive destruction of granulocytes (immune and non-immune), and abnormal distribution of granulocytes.
Although the clinical symptoms of leukopenia are similar, however, the causes of leukopenia are different and their treatment varies, so the cause should be actively sought after the diagnosis of leukopenia. The disease is associated with infection, physical and chemical factors, hematopoietic disorders, immune system disorders, hepatosplenomegaly, and genetics.
1, Infection: Bacterial, viral, rickettsial and protozoal infections can cause leukopenia.
2, physical and chemical factors: radiation, nuclides, certain organic solvents and certain drugs such as anticancer drugs, antipyretic and analgesic drugs, sulfonamides, antithyroid drugs, anticonvulsants, antihistamines, antibiotics, etc. can cause leukopenia or granulocyte deficiency.
3, blood diseases: aplastic anemia, pernicious anemia, multiple myeloma, lymphoma, acute and chronic leukemia, bone marrow metastases, etc. can cause leukocytopenia.
4, immune diseases: such as systemic lupus erythematosus, rheumatoid arthritis, etc.
5, other: cirrhosis (after hepatitis), hypersplenism, congenital granulocytopenia, granulocytopenia with congenital defects or with abnormal globulin, familial benign granulocytopenia, cyclic granulocytopenia, chronic primary granulocytopenia, etc.
Clinical manifestations and laboratory tests
1.Clinical manifestations
The clinical manifestations often vary with the causative factors and the degree of leukopenia. A small number of patients are asymptomatic and are only detected during blood tests. Most patients have dizziness, fatigue, often accompanied by loss of appetite, limb weakness, insomnia and dreaminess, low fever, palpitations, chills, lumbago and other symptoms, sometimes prone to infectious diseases. In the case of granulocyte deficiency, infection often occurs and the condition is more dangerous. It is accompanied by fever, chill, sore throat, etc., and even causes sepsis.
2. Laboratory tests
(1) Blood routine: granulocyte deficiency leukocytes generally fall below 2.0×109/L, granulocytes <0.5×109/L, granulocyte cytoplasm can be seen in toxic particles, granulocyte alkaline phosphatase is elevated, lymphocytes and monocytes are relatively increased in blood.
(2) Bone marrow examination: If the proliferation is obviously active or extremely active, it indicates that the granulocyte lineage is ineffective or destroyed too much; if the proliferation is low or active, the granulocyte lineage is reduced in the early stage, and a certain amount of middle and late juvenile granulocytes and a few primitive and early juvenile granulocytes can be seen. In the late stage, the granulocyte lineage is severely depressed, and only a few young red blood cells, lymphocytes, plasma cells and reticulocytes are seen.
(3) Epinephrine test: It is used to understand the distribution of granulocytes in the limbic pool and circulating pool. Within 20-30 minutes after subcutaneous injection of 0.1% epinephrine 0.3 ml, if the granulocytes increase to one times the original level or increase by 3×109/L, and the patient does not have splenomegaly, it indicates “pseudo-granulocytopenia” with increased granulocytes in the marginal pool.
(4) Prednisolone test: This test is a test of bone marrow reserve capacity. Oral prednisolone 40mg, the normal response to the peak 5 hours after taking, granulocytes should be greater than 2 × 109 / L. Or with hydrocortisone 200mg intravenous 3 ~ 4h after the increase in white blood cell count than before the drug (4 ~ 5) × 109 / L is normal. Otherwise, it is considered insufficient storage or release disorder.
III. Differential diagnosis
The disease needs to be differentiated from acute leukemia with leukopenia and aplastic anemia. The latter two are accompanied by anemia and thrombocytopenia, and bone marrow aspiration is an important basis for differentiation.
IV. Treatment.
1. Patients with granulocyte deficiency are often combined with severe infections, even for sepsis and septicemia leading to death. Put the patient in a sterile ward or laminar flow ward, take strict disinfection and isolation measures to prevent secondary infection; patient’s utensils, food, etc. need to be sterilized; strengthen the patient’s skin, oral cavity, perianal, vaginal care; for suspected bacterial infection, repeatedly send throat swabs, blood, urine, fecal culture plus drug sensitivity test; strengthen supportive therapy to promote granulocyte recovery as soon as possible. Once the patient has fever that should be done blood, urine and other relevant bacterial culture, and according to experience, heavy-handed, choose broad-spectrum antibiotics, early, combined, adequate, intravenous administration, and select targeted antibiotics after the return of bacteriological results; at the same time, pay attention to the prevention and control of secondary infections, such as mycobacterial, anaerobic infection. Some experts and scholars believe that antibiotics should be used prophylactically in granulomatous deficient states, although they cannot significantly reduce the incidence of nosocomial infections in granulomatous patients. Glucocorticoids can improve the general condition of the body and restore the proliferation of granulocytes, but these drugs have the risk of causing infection and aggravating infection, and short-term application, such as short-term application of prednisone 40-60 mg/d, is recommended. recovery of granulocytes. The usual use is 300ug/d until granulocytes are greater than 1.0×109/L or for 7-14 days. Gammaglobulin is also beneficial for the control of infection during granulocyte deficiency.
The key to the treatment of leukopenia is to actively seek and remove the causative factors, discontinue suspected drugs and remove toxic exposure, and prevent and treat infections. For long-term follow-up blood image stability and no infection generally do not need drug therapy. The following measures can be used for specific treatment as appropriate.
(1) General care: pay attention to nutrition, supply all kinds of B vitamins and vitamin C. In case of coexistence with nutritional megaloblastic anemia, supplementation with folic acid and vitamin B12 can be used.
(2) Anti-infection treatment: Once the patient has fever, blood, urine and other relevant bacterial cultures should be done immediately, and broad-spectrum antibiotics should be given, and then changed to targeted preparations after the pathogen of infection is confirmed. If the pathogen is not confirmed then the empirical intravenous treatment with broad-spectrum antibiotics must be given for a full course of treatment.
(3) Glucocorticoids: These drugs are limited to the treatment of immune granulocytopenia, and generally cannot be used alone. The commonly used drug is prednisone 30~40mg/day. Long-term application is prone to complications of infection.
(4) Cell growth factor: It can accelerate the recovery of chemotherapy-induced leukopenia, prevent strong chemotherapy-induced leukopenia and fever, and also treat congenital granulocytopenia. The side effects of CSF include fever and chills, bone and joint pain, etc.
(5) Leukocyte growth stimulating drugs: There are many kinds of drugs that can enhance leukocytes, and most of them are temporary in effect. Generally, two to three drugs can be used in combination with each other. After 3~4 weeks of ineffective treatment, you can switch to other drugs. The more commonly used drugs are: ①Vitamin B4: 20~40mg each time, 3 times a day. ②Inosine: 0.2~0.6g each time, 1~2 times a day. ③Lixin: 10~20mg each time, 3 times a day. ④Lithium carbonate: 20~30mg each time, 3 times daily for 4~6 weeks. ⑤ Shark’s liver alcohol: 20mg each time, 3 times daily, 4~6 weeks as a course of treatment.
V. Traditional Chinese medicine
This disease belongs to the category of “deficiency labor” in Chinese medicine, which is considered to be caused by congenital deficiency of endowment, acquired disorder, long term illness or poisoning by certain chemical toxins. The deficiency of congenital endowment, acquired disorders or overwork can lead to deficiency of the spleen and kidney and insufficient biochemistry of qi and blood. In short, this disease is based on deficiency, or deficiency causes disease, because of disease into labor; or because of disease into deficiency, long deficiency does not return into labor. The deficiency of qi and blood, the imbalance of yin and yang, and the impairment of heart, liver, spleen, and kidney functions are the key to its development. The general principle of treatment is to mainly tonic, and at the same time to eliminate evil.
1.Treatment by identification
(1) Heart and spleen deficiency
Main symptoms: lassitude, palpitation, dizziness, insomnia, sleeplessness, abdominal distension, pale tongue, thin white fur, thin pulse.
Analysis: The spleen is the master of transportation and transformation. If the spleen is not healthy, the abdomen will be distended; the spleen is the master of muscles and limbs. If the heart and spleen are deficient in qi, the qi will not be carried upward, so dizziness, light tongue and thin pulse are all signs of qi deficiency. The location of the disease is in the heart and spleen, and the nature of the disease is deficiency. Palpitations and weakness, insomnia and dullness are the main points of differentiation of this evidence.
Treatment: Tonify Qi and Blood, strengthen the spleen and nourish the heart.
Formula: Gui Shen Tang with addition and subtraction.
Radix et Rhizoma Ginseng 12g, Radix Astragali 20g, Radix Angelicae Sinensis 12g, Rhizoma Atractylodes Macrocephalae 12g, Fu Shen 12g, Yuan Zhi 12g, Longan 15g, Mu Xiang 6g, Radix Bupleurum 15g, Radix Chrysanthemum 30g, Radix Paeoniae Alba 15g, Radix Polygalae Sinensis 15g, Jujube 10.
(2) Spleen and Kidney Yang Deficiency
Main symptoms: fatigue, soreness and weakness of the waist and knees, cold in the extremities, abdominal distension and loose stools, dizziness and tinnitus, pale fat tongue, thin white fur, sunken weak pulse.
Analysis: The spleen is the source of Qi and blood biochemistry; the kidney collects essence and is responsible for the Yang energy of the body. The disease is located in the spleen and kidney, and the nature of the disease is deficiency. Cold fear, weakness and loose stools are the main points of identification of this disease.
Treatment: Warming the middle and strengthening the spleen, benefiting the kidney and filling the essence.
Radicals: combining Right Return Pill with Radix Rehmanniae Pill, plus and minus.
The formula includes 10g of Radix Aconiti (decoction first), 10g of Ginseng, 15g of Atractylodes Macrocephala, 15g of Radix Rehmanniae Sinensis, 12g of Yam, 12g of Cornu Cervi Pantotrichum, 15g of Fructus Lycii, 15g of Semen Cuscutae, 12g of Radix Angelicae Sinensis, 12g of Colla Corii Asini, 12g of Roasted Licorice.
(3) Liver and Kidney Yin Deficiency
Main symptoms: dizziness and blurred vision, lumbar soreness and leg weakness, irritable heat in the five hearts, dryness of the mouth and throat, red tongue with little coating, thin and slightly counted pulse.
Analysis: Kidney stores essence, liver stores blood. Dizziness, soreness and weakness of the waist and knees, and irritability and heat of the five hearts are the main points of identification of this evidence.
Treatment: Nourish the liver and kidney, tonify the qi and benefit the essence.
Formula: Tai Teng Yuan Decoction with reduction.
Radix et Rhizoma Ginseng 20g, Radix Rehmanniae 15g, Rhizoma Yam 12g, Cortex Eucommiae 12g, Fructus Lycii 15g, Cornu Cervi Pantotrichum 15g, Rhizoma Polygonatum 15g, Radix Angelicae Sinensis 15g, Radix Glycyrrhiza Uralensis 12g.
(4) Warmth and heat with incandescence.
Main manifestations: strong heat and cold, or high fever and chills, head and body pain, extreme fatigue, sore throat and thirst, short urination, red tongue with little fluid, yellow fur, pulse count.
Analysis of the evidence: deficiency of vital energy, combined with heat and poisonous evil, resulting in fever and chills, headache and body pain; sore throat due to heat attacking the upper jiao; thirst, red urine and red tongue with little fluid are due to heat depletion of fluid; strong heat and food, resulting in extreme fatigue; yellow moss and number of pulses are symbols of heat. The cough with yellow sputum and oral erosion can be seen when the heat penetrates into the internal organs. This is a manifestation of granulocyte deficiency with infection. The location of the disease is in the qi division, and the nature of the disease is deficiency. High fever and coldness, extreme fatigue are the main points of identification. It is appropriate to treat the symptoms with urgency.
Treatment: Pungent and cool to penetrate the surface, clear heat and detoxify.
Formula: Yin Qiao San combined with Five Flavors Disinfectant Drink plus or minus.
Jin Yin Hua 30g, Wild Chrysanthemum 15g, Dandelion 15g, Di Ding 15g, Forsythia 15g, Burdock 15g, Radix Platycodon 12g, Tiger Balm 30g Cockscomb 20g Licorice 12g
2. Prepared Chinese medicines
(1) Ginseng and Spleen Pill: 1 pill each time, 2 to 3 times a day. Suitable for people with deficiency of both heart and spleen.
(2) Diyu Shengbai Tablets: Effective in preventing and treating granulocytopenia and deficiency caused by anticipatory reactions to granulocytopenic drugs. 2-4 tablets per time, 3 times/d, 20-30 days as a course of treatment.
(3) Zhenqi Punch: 1 sachet each time, 2-3 times daily. It is suitable for leukopenia after chemoradiotherapy.
(4) Compound soap alum pill: composed of soap alum, American ginseng, seahorse, cinnamon, jujube and walnut. It is used for the treatment of bone marrow damage caused by radiotherapy and chemotherapy for tumor and acute leukemia, and leukopenia associated with hyperthyroidism. The dose is 9 capsules each time, 3 times/d, the course of treatment is 1 to 3 weeks
VI. Treatment experience.
1, the disease is centered on the deficiency of heart, spleen, liver and kidney, and the prescription can be chosen flexibly according to the severity of the damage of each organ. In addition, the method of promoting Qi and Blood also has certain curative effect.
On the basis of evidence-based treatment, several herbs can be used to raise leukocytes, such as Astragalus, Atractylodes, Radix Bupleuri, Radix et Rhizoma, Radix Rehmanniae, Radix Rehmanniae, and Jujube.
3, granulocyte deficiency combined with infection is a warm-heat incandescence, the emergency is to treat its symptoms, combined treatment of Chinese and Western medicine, after the infection is controlled, it is appropriate to treat its root, when the evidence-based treatment.