Leukopenia is defined as a persistent peripheral blood leukocyte count below the low limit of the reference value, which is below 4.0 × 10 9/L in adults; this condition is mainly due to neutropenia. When the absolute neutrophil count (ANC) is below 2.0×10 9/L, it is called granulocytopenia, and when the ANC is <0.5×10 9/L, it is called granulocyte deficiency. There is a clear relationship between the degree of neutropenia and its duration and the risk of infection.
I. Etiology and pathogenesis
1. Granulocyte proliferation or maturation disorders
Aplastic anemia, infections, X-rays, gamma rays, chemicals such as benzene and xylene, and drugs are among the most common and important causes of impaired bone marrow granulopoiesis, mainly including antineoplastic drugs as well as antipyretics, sedatives, chloramphenicol, sulfonamides, antithyroids, antihistamines, hypoglycemic drugs, cardiovascular drugs and diuretics.
Megaloblastic anemia, myelodysplastic syndrome, and the application of antimetabolic drugs (methotrexate, 6-mercaptopurine, etc.) and antithyroid drugs (tapazole, thioredoxin, etc.) can cause impaired granulocyte maturation and ineffective generation (excessive apoptosis).
2. Excessive destruction or depletion of granulocytes
The presence of granulocyte antibodies in the blood caused by connective tissue diseases, autoimmune diseases, and the use of drugs such as aminopyrine, methyldopa, and sulfathiazole causes immune granulocytopenia. Diseases such as hypersplenism cause excessive retention and destruction of granulocytes in the monocyte-macrophage system. Granulocytes in the blood are increased and consumed faster due to severe infections and other entry into tissues, and granulocyte destruction is increased in protozoa, rickettsia and viral infections.
3.Abnormal distribution of granulocytes
Anaphylaxis, allogeneic protein reaction, viraemia, etc. cause excessive transfer of granulocytes to the limbic pool, and the granulocytes in the circulating pool are reduced, but the total number of white blood cells remains unchanged, which is called pseudogranulocytopenia.
II. Clinical manifestations
1. Leukopenia.
There are differences in the severity of symptoms depending on the degree of neutropenia. Dizziness and malaise are the most common, and symptoms such as loss of appetite, insomnia and hypothermia may also be present. The susceptibility of patients to infections varies greatly among individuals, and some patients do not necessarily have frequent infections, while others may have upper respiratory tract infections, stomatitis, bronchitis, pneumonia, otitis media, and urinary tract infections. If there is mononucleosis, there is usually no serious infection.
2. Granulocyte deficiency.
The onset is mostly acute, with the main symptoms being chills, high fever, headache, and peripheral discomfort, often accompanied by necrotic ulcers in the gums, oral mucosa, tongue, pharynx, and other mucosal areas. There may be submandibular and cervical lymph node enlargement, and a few patients develop jaundice and liver and spleen enlargement, which may cause serious lung infection and sepsis.
Differential diagnosis
1. Aplastic anemia
With anemia and thrombocytopenia, there is usually no enlargement of liver, spleen and lymph nodes, and bone marrow examination can be differentiated.
2.Myelodysplastic syndrome
Most commonly seen in the elderly. Peripheral blood has trilineage reduction, bone marrow pathological hematopoiesis, often with chromosomal abnormalities, bone marrow examination can help differentiate.
3.Leukemia
Especially leukocytic non-leukemic leukemia, often accompanied by anemia and bleeding symptoms, bone marrow examination can identify.
III. Treatment plan
1.Remove the cause or trigger
Stop taking the relevant drugs if they are caused by drugs, stop radiation exposure if they are exposed to radiation, and actively treat the original disease if they have the original disease.
2. Disinfection and isolation measures
Strengthen skin, oral, anal and vaginal care to prevent cross-infection. Those with granulocyte deficiency should take strict disinfection and isolation measures, indoor utensils, food, etc. should be sterilized. Antibiotics should be used early in case of infection.
3. Drugs to increase white blood cells
(1) Lixisen 20mg, orally, 3 times daily.
(2) Shark liver alcohol 50mg, orally, 3 times a day.
(3) Lithium carbonate 0.3g, orally, 3 times a day.
(4) Vitamin B4 10mg, orally, 3 times daily.
(5) Inosine tablets 0.2, orally, 3 times a day.
The above mentioned drugs have slow effect in raising leukocytes, and their efficacy is not exact.
4.Glucocorticoids
For those who suspect leukopenia caused by immune factors and the general leukocyte-raising drugs are ineffective. Prednisone 10mg, orally, 3 times daily. Discontinue for 4 weeks to avoid aggravating infection.
5.Hematopoietic growth factor
rhG-CSF or rhGM-CSF is a special drug to promote granulocyte production, prolong the life span of granulocytes and enhance the body’s ability to resist infection. Usage: 75–150μg/d, subcutaneous injection, usually 3 days after rechecking the blood routine white blood cells can be restored to normal. This drug is generally not used before and during chemotherapy, and is mostly used for those with reduced leukocytes after chemotherapy.
IV. Prognosis
In the past, the mortality rate of acute granulocyte deficiency was as high as 75% – 90%, but after the adoption of aseptic isolation measures, antibiotics and the widespread use of hematopoietic growth factors, the mortality rate has been reduced to less than 25%. The prognosis is poor in elderly, systemic failure, jaundice combined with severe infection, severe depressed bone marrow neutrophilia, and those who do not improve significantly even after 10 days of active treatment.