Overview of leukopenia
A persistent peripheral blood leukocyte count of <4 × 109/L in adults is called leukopenia, and an absolute peripheral blood neutrophil count of <2.0 × 109/L in adults is considered granulocytopenia, and <0.5 × 109/L is considered granulocyte deficiency.
Etiology
Leukopenia and/or granulocytopenia primary (cause unknown) is rare, mostly secondary. Common pathogenic mechanisms are: ① reduction of granulocyte production, such as infection, ionizing radiation, bone marrow metastasis of tumors, malignant hematologic diseases, anti-tumor or other drug effects, etc.; ② granulocyte maturation disorders in megaloblastic anemia, myelodysplastic syndromes, etc.; ③ increase in granulocyte destruction, such as hyper-splenism, infections, inflammation, or immune abnormalities; ④ granulocyte distribution abnormality Granulocytes in the circulating pool of the granulocytes migrate to the edge of the pool, which may The migration of granulocytes from the circulating pool to the marginal pool may cause pseudo-granulocytopenia and a decrease in peripheral blood granulocyte count. After injection of adrenal hormone, granulocytes enter the circulating pool from the marginal pool, and the count returns to normal.
Symptoms
Leukopenia is often secondary to a variety of systemic diseases, and the clinical manifestations are dominated by the primary disease. Most patients have a slow onset of the disease and may present with dizziness, fatigue, palpitations, low-grade fever, insomnia, pharyngolaryngitis and mucosal ulcers. Neutrophils are the body’s first line of defense against pathogenic microorganisms, and thus the clinical symptoms of granulocytopenia are mainly susceptible to recurrent infections. The patient’s risk of developing infections is directly related to the number of neutrophil counts, the rate of decrease, and the degree of impairment of the rest of the immune system. Chronic primary neutropenia is seen in both children and adults, with mild or no infections, and resolves spontaneously within a year in most patients, with a few lasting for years. Cyclic neutropenia can occur at any age, but is more common in children, the course of the disease is prolonged for many years, with a certain regularity of episodes, often at intervals of 21 days (12-35 days), each lasting 3-6 days, with episodes of generalized malaise, headache, fever, with pharyngeal or other parts of the infection, and in some cases, arthralgia, splenic and lymph node enlargement. Drug-induced granulocytopenia most often occurs 5 weeks after the use of drugs, the longest can be up to 7 weeks, but can also be onset within a few hours, the clinical manifestations are mainly fatigue, easy to fatigue, severe cases can be chills, sore throat, pneumonia, fever, bone pain, and so on.
Examination
1. Blood picture
It shows a decrease in white blood cell and neutrophil counts.
2. Bone marrow
It can understand the proliferation and maturation of granulocytes, and sometimes it can clarify whether there is tumor cell metastasis, leukemia, myelodysplastic syndrome and other hematologic diseases.
3. Examination related to primary disease
If connective tissue disease is suspected, corresponding immunological examination should be performed.
4. Determination of anti-neutrophil antibodies
If the patient is positive for anti-neutrophil antibodies and negative for anti-human leukocyte antigen (HLA), it is suggestive of autoimmune neonatal neutropenia and acquired autoimmune neutropenia.
5. Measurement of granulocyte kinetics and lifespan
Granulocytes labeled with radiolabeled isoflurane phosphorus (DF32P) can be used for measurement, which is the most reliable index to understand the conversion of neutrophils, but the technical equipment requirements are high, and it is difficult to popularize.
6. Adrenaline test
Epinephrine 0.3mg, subcutaneous injection, 20 minutes before and after the injection, do a white blood cell count once, if the absolute value of granulocytes increased to more than one times before the injection, and the patient does not have splenomegaly, then it is positive, indicating that the patient may be pseudogranulocytopenia, the granulocytes of the circulating pool migrate to the marginal pool.
Diagnosis
1. Leukopenia
Adults: peripheral blood leukocyte count below 4.0×109/L;
Children: less than 4.5×109/L above 10 years of age and less than 5.0×109/L below 10 years of age.
2. Granulocyte deficiency
Severe reduction of peripheral blood neutrophils with an absolute value of less than 0.5×109/L.
The diagnosis of leukopenia and granulocyte deficiency is based on the decrease of peripheral blood leukocytes, which must be determined by the age of the patient; and finger blood should be taken, preferably venous blood for counting, more than two consecutive checks, and the time of blood collection should be fixed at the same point of time on a certain day. The diagnosis can only be confirmed by eliminating errors in blood collection, physiological fluctuations of leukocytes at different times and testing errors.
Treatment
1. Remove the cause of the disease
Remove all factors that may lead to leukopenia and granulocytopenia as far as possible; treat the primary disease, e.g. cut the license plate for patients with hypersplenism.
2. Long-term follow-up
If the blood picture is stable and no infection occurs, treatment is usually not needed.
3. Use of antibiotics
The main manifestation of neutropenia is infection, but the risk of infection is negatively correlated with the degree of neutropenia. Attention should be paid to maintaining oral, gum and skin hygiene to reduce recurrent infections, but the prophylactic use of antibiotics is generally not advocated. If infection occurs, empirical broad-spectrum antibiotics should be given immediately after pathogenetic examination, and antibiotics should be adjusted according to the results of pathogenetic examination and drug sensitivity test.
4. Colony-stimulating factor
Granulocyte stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are the most effective granulocyte-boosting drugs so far.
5. Other drugs that stimulate leukocyte growth
There are many kinds of drugs, including vitamin B4, B6, lisdexamfetamine, aminopeptide, shark liver alcohol, inosine (according to the regular dose of drugs) and lithium carbonate, etc., but all of them lack of certainty and long-lasting efficacy.
6. Immunosuppressants
For patients diagnosed with immune granulocytopenia or cytotoxic T-cell-mediated bone marrow failure, glucocorticoids, azathioprine, cyclophosphamide, and high-dose gammaglobulin can be used.
7. Granulocyte infusion
Generally, prophylactic transfusion is not necessary, and can be applied when the following three conditions exist simultaneously: granulocyte deficiency (<0.5×109/L); accompanied by severe infection; and ineffectiveness of advanced antibiotic treatment for 48 hours.
8. Hematopoietic stem cell transplantation
Due to the high mortality rate associated with allogeneic hematopoietic stem cell transplantation, the advantages and disadvantages should be weighed, the indications should be well mastered, and the option should be considered only for those with serious conditions.