Pediatric drug-induced hemolytic anemia

Introduction to pediatric drug-induced hemolytic anemia Drug-induced hemolytic anemia (drug-induced hemolytic anemia) can be divided into four categories according to reasons: drug-induced erythrocyte enzyme deficiency hemolytic anemia. The drug induces hemolytic anemia of unstable hemoglobin. Hemolytic anemia caused directly by the drug or its toxicity. Drug-induced immune hemolytic anemia. Among them, drug-induced immune hemolysis is more common. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: renal failure

Pediatric drug-induced etiology of hemolytic anemia

(1) Causes of the disease

There are many drugs that can induce immune hemolysis, such as penicillins, sulfonamides, rifampicin, isoniazid, p-aminosalicylic acid, phenacetin, quinine, quinidine, alpha methyldopa, Levodopa, phenytoin, chlorpromazine, chlordiazepoxide, aminopyrine, antazoline, cefotaxime, ceftazidime, ceftriaxone, chlorambucil (tumoren), An Nai near , insecticide, , podophyllotoxin, thiazide, carboplatin, cisplatin and so on.

(two) pathogenesis

According to the mechanism of occurrence, drug-induced immune hemolysis is divided into the following four types:

1. hapten type (penicillin type): Since the body produces an anti-drug (such as penicillin) antibody that binds to red blood cells, thereby exposing the hapten of the drug, the antibody can bind to the red blood cell-drug, and the red blood cells are conditioned. In the spleen, it is destroyed by mononuclear macrophages, so it is mostly extravascular hemolysis. In the case of penicillin, in patients treated with lower doses, hemolysis does not occur, and the direct Coombs test is rarely positive. Because low-affinity IgG-type anti-penicillin antibodies are common, hemolysis occurs only when the serum concentration is extremely high (more than 20 million U per day), and hemolysis is often mild, and occasionally acute hemolysis can occur. After stopping the drug, hemolysis Anemia also stops quickly.

2. Immune complex type (Quinidine type): Some drugs or their metabolites can bind to plasma proteins to form immunogenic complexes, producing drug antibodies (mostly IgM) and drug-plasma proteins. Combines into a complex and adheres to red blood cells, which causes hemolysis by activating complement. This immune complex can be separated from the red blood cell membrane and adsorbed on another red blood cell membrane, so a small amount of drug can cause a large number of red blood cell destruction, resulting in Intravascular hemolysis, anti-human globulin test positive, mostly complement type, common drugs of this type are quinine, quinidine, phenacetin, sulfa drugs, chlorpromazine, isoniazid, chlorpropamide Wait.

3. Autoantibody type (-methyldopa type): Drug-induced antibodies can react with normal erythrocyte surface antigens, specifically targeting Rh-positive erythrocyte membranes, and direct Coomb test (DAT) is generally used. It can only be converted to positive in months or even years. After the patients with hemolysis are stopped, hemolysis can be stopped, autoantibodies can gradually disappear, DAT or indirect Coomb test (IAT) is positive without the participation of drugs, and -methyldopa treatment Patients often have antinuclear antibodies, rheumatoid factor and anti-wall cell antibodies. When hemolysis occurs, red blood cells are mostly destroyed in the mononuclear macrophage system. The mechanism may be that T inhibits cell function inhibition, thereby enhancing B cell function. , producing different autoantibodies.

4. Mixed type: It means that the occurrence of hemolysis is caused by more than one mechanism. For example, streptomycin is a hapten, which can strongly bind to M antigen or D antigen on erythrocyte membrane to produce penicillin-type hemolysis, and can also produce binding. Complementary IgG antibody causes intravascular hemolysis, and penicillin can cause immune complex type hemolysis or quinine-induced hemomycin-type hemolysis, which has been reported clinically. In addition, some patients have immunogenic drug-erythrocyte formation. Particularly sensitive to certain drugs, the specificity of this drug antibody comes not only from the drug itself, but also from red blood cell antigens, especially the Rhesus and I/i antigen systems.

Pediatric drug-induced hemolytic anemia prevention

Drugs that can induce this disease should strictly control the indications and reasonable doses in clinical use, and improve the vigilance of the occurrence of the disease, closely monitor, and immediately stop the drug once found; according to the condition, take corresponding treatment measures to avoid the disease worse.

Pediatric drug-induced complications of hemolytic anemia Complications, renal failure

Severe can be complicated by hemoglobinemia and hemoglobinuria, renal failure, DTC. A small number of concurrent granulocytes and platelets are reduced.

Symptoms of hemolytic anemia induced by pediatric drugs Common symptoms Elevated bilirubin Red blood cells Low immune hemolytic granulocytes reduced hemoglobinuria Thrombocytopenia Renal failure Intravascular coagulation

Hemolysis caused by penicillin occurs mostly in the continuous application of a large amount of penicillin for more than 1 week. Most of the hemolysis is lighter. In severe cases, hemoglobin can be rapidly decreased, reticulocytes are elevated, and cefotaxime can cause similar reactions, but the dose is not large. Such patients have a history of previous medications, and some patients have occurred during long-term medication. Generally, hemolysis can disappear after a few days or weeks of withdrawal. Hemolysis caused by -methyldopa occurs in medications 3-6. Months or more, hemolysis is lighter, disappears after 1 to 2 weeks of withdrawal, quinidine-type hemolysis is acute, anemia is severe, accompanied by hemoglobinemia and hemoglobinuria, renal failure is common, and a few are diffuse Intravascular coagulation, a small number of children may have granulocytes or platelets reduced, after stopping the relevant drugs, the blood can return to normal within 1 to 2 weeks, the above 3 types of hemolytic anemia, in addition to clinical characteristics are not the same, anti-human globulin The test can help identify.

Pediatric drug-induced examination of hemolytic anemia

1. Blood: peripheral blood hemoglobin and red blood cells decreased; serum bilirubin increased mainly by indirect bilirubin.

2. Urine examination: When hemoglobinuria, creatinine and urea nitrogen are elevated, it indicates impaired renal function.

3. Coombs test: Direct Coombs test positive; positive Coombs test positive or positive after incubation of related drugs.

4. Anti-human globulin test can help identify.

5. X-ray chest X-ray, B-ultrasound, etc. should be routinely performed.

Diagnosis and diagnosis of hemolytic anemia induced by pediatric drugs

diagnosis

Diagnosis can be based on the cause, symptoms and related tests.

Differential diagnosis

1. Autoimmune hemolytic anemia (cold antibody type and warm antibody type): The main difference between the hapten type of the disease and the disease is that the former serum antibody reacts only with the drug-coated red blood cells, plus the history of drug exposure. It is decisive for the differential diagnosis between the two. The immune complex type was positive for the direct Coombs test against anti-complement serum, similar to the cold antibody type autoimmune hemolytic anemia, but the former combined with the cold agglutinin test and the DL test negative, plus the indirect Coombs test was only incubated with the relevant drugs. Positive, direct Coombs test turned negative after stopping the drug, it is not difficult to clearly identify the diagnosis between the two. The -methyldopa-induced autoimmune hemolytic anemia, directly Coombs test positive (IgG type), usually showed Rh antigen specificity, and was also positive for the modified red blood cell indirect Coombs test. There is no specific serological test to distinguish it from warm-antibody autoimmune hemolytic anemia, but the diagnosis of anemia is supported by the anemia recovery and antibody disappearance after discontinuation of related drugs.

2. Congenital hemolytic anemia (such as hereditary spherocytosis): This disease is a family hereditary hemolytic disease, the clinical features of which are varying degrees of hemolytic anemia, intermittent jaundice, splenomegaly and splenectomy Can significantly improve symptoms.

3. It is also necessary to distinguish between hemolytic anemia associated with drugs that occur due to erythrocyte metabolic diseases such as G-6-PD deficiency.

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