Secondary immune thrombocytopenic purpura in children

Introduction to secondary immune thrombocytopenic purpura in children Due to immune-mediated secondary thrombocytopenic purpura, such as drug-induced immune thrombocytopenia, other immune thrombocytopenia such as Evans syndrome, systemic lupus erythematosus, rheumatoid arthritis, hyperthyroidism Wait. Here, we focus on the secondary thrombocytopenic purpura, drug-induced thrombocytopenic purpura (drugs inducedimmunethrombocytopenicpurpura), and a variety of drugs, mainly hapten-induced drugs, which cause thrombocytopenia through immune mechanisms. Drug-induced thrombocytopenia. basic knowledge The proportion of illness: 0.003% Susceptible people: children Mode of infection: non-infectious Complications: intracranial hemorrhage, hematuria, acute renal failure

Secondary immune thrombocytopenic purpura in children

(1) Causes of the disease

1. Infection: Viral infection can cause a mild to moderate decrease in platelets, which is caused by the virus inhibiting the production of platelets by megakaryocytes and shortening the lifespan of platelets.

2. Aplastic disorders: low bone marrow hyperplasia, first thrombocytopenia, and then red blood cell line and granulocyte cell proliferation is low.

3. Myelodysplastic abnormalities: the earliest occurrence of megakaryocytes reduced thrombocytopenia, followed by red blood cell line, granulocyte-monocyte lineage hematopoiesis.

4. Bone marrow occupying lesions: Some malignant tumors invade the bone marrow to reduce megakaryocyte production and inhibit their maturation, showing thrombocytopenia, such as leukemia, malignant lymphoma, and cancer metastasis.

5. Drug causes:

(1) Antipyretic analgesics: antipyrine, aspirin, sodium salicylate, acetaminophen (paracetamol), indomethacin (indomethacin), phenylbutazone, etc.

(2) Antibiotics: penicillin, sulfonamides, cephalosporins, tetracyclines, erythromycin, anti-tuberculosis drugs and chloroquine.

(3) antispasmodic sedative drugs: barbiturates, chlorpromazine, diazepam, phenytoin, trifluoperazine, pethidine (degree cold), codeine, chlorpheniramine (chlorpheniramine), right Amphetamine and the like.

(4) Cardiovascular drugs: lishepine, quinine and quinidine, digitalis, nitroglycerin, methyldopa, diazoxide, etc.

(5) Diuretics: hydrochlorothiazide, spironolactone, diuretics containing mercury, etc.

(6) Others: gold preparation, ergot, potassium iodide, heparin, propylthiouracil, cimetidine and the like.

(two) pathogenesis

According to the pathogenesis, the onset of immune thrombocytopenic purpura can be divided into platelet production, abnormal platelet distribution, excessive platelet destruction and platelet dilution.

1. Thrombocytopenia Reduced thrombocytopenia: characterized by a decrease in the number of megakaryocytes in the bone marrow, and a correspondingly low number of platelet production and platelet turnover.

(1) Infectious thrombocytopenia: Viral infection can cause a mild to moderate decrease in platelets, which is caused by the virus inhibiting the production of platelets by megakaryocytes and shortening the lifespan of platelets, such as aplastic anemia after hepatitis, which may damage the bone marrow or itself with hepatitis virus. Immune-related, at this time should mainly treat the primary disease, can take vitamin C, rutin, kabakol (Anluo blood), phenolsulfonamide (hemostatic), aminopeptin and other drugs to improve capillary fragility, Patients with severe bleeding can use corticosteroids for a short period of time.

(2) aplastic anemia: aplastic anemia can first appear thrombocytopenia, and then the erythrocyte and granulocyte cell proliferation is low, the treatment is mainly used to stimulate bone marrow hyperplasia drugs, such as sagstatin (white energy, GM- CsF) and erythropoietin (Epo) can also be used with immunosuppressive drugs such as adrenocortical hormone, testosterone propionate, antithymocyte or anti-lymphocyte globulin.

(3) Myelodysplastic syndrome (MDS): the earliest megakaryocyte reduction leads to thrombocytopenia, followed by red blood cell line, granulocyte-monocyte lineage hematopoiesis, diagnosis, except for bone marrow puncture, showing one or two lines of pathological hematopoiesis It should be used for stem cell culture, chromosome examination, and treatment to stimulate hematopoiesis and induce differentiation agents according to different stages.

(4) Bone marrow occupying lesions: some malignant tumors invade the bone marrow to reduce megakaryocyte production and inhibit its maturation, showing thrombocytopenia, such as leukemia, malignant lymphoma, cancer metastasis, etc., clinical symptoms and bleeding. In the course of the disease, the platelets can be restored to normal with the disease, and the treatment is mainly combined with chemotherapy.

2. Increased platelet destruction caused by thrombocytopenia

(1) Drugs-induced thrombocytopenia (drugs induced immune thrompocytopenia): mainly refers to the binding of certain hapten drugs or drug metabolites to plasma macromolecular proteins, or adsorption to platelet membrane-forming antigen complexes, resulting in corresponding Antibodies (mainly IgG, followed by IgM), antigen-antibody complex attached to the surface of platelets in the presence of complement or directly damage platelets, resulting in platelet aggregation, destruction, removal by mononuclear macrophages, thrombocytopenia, known molecular weight A drug of 500 to 1000 Da can be used as a hapten in combination with one or more protein components of a platelet membrane to form an antigen and stimulate the body to produce a specific antibody which is specific to the drug-platelet complex and can be directly Some components of platelets, such as membrane glycoproteins GP1b/IX and GPIIb/IIIa, are eliminated by the mononuclear-macrophage system, and some can directly activate the complement system to cause platelet destruction.

1 drug inhibitory thrombocytopenia (drug inhibitory thrombocytopenia): these drugs are the most common and serious anti-tumor chemotherapy drugs, it not only inhibits the formation of platelets, but also has a significant inhibitory effect on the granulocyte system, and The inhibition of granulocytes is more obvious. The most serious threat to the clinic is the infection caused by neutropenia, not the thrombocytopenia caused by drug inhibition. The bleeding is often mild and rarely causes serious viscera. Bleeding, generally does not require special treatment, but when the number of platelets is too low, such as below 20 × 109 / L (20,000 / mm3), in order to prevent intracranial hemorrhage, should also be infused with platelet suspension (each 1U / 7kg ) or fresh whole blood (10 ~ 20ml / kg each time).

2 drug immune thrombocytopenia (drug immune thmrombocytopenia): drugs that cause immune thrombocytopenia into the body, combined with plasma proteins, macromolecular substances or platelet membrane components to form antigens, thereby stimulating the body to produce antibodies, when again When the corresponding drugs are taken, the immune platelets are destroyed due to the immune reaction. Although the mechanism of forming antibodies and immune responses is different, the clinical manifestations are similar, and the symptoms appear irrespective of the dose, and are related to the re-medication. Immediately after taking the drug (usually within 1 day), thrombocytopenia and hemorrhage occur, which is manifested as skin blemishes or ecchymosis, mucosal bleeding, severe cases may have digestive tract, urinary tract bleeding, if it can be stopped in time, often Within a few days, the bleeding stopped, and the platelets returned to normal within a few weeks. The principle of treating drug-induced thrombocytopenia was basically the same as that of drug-induced thrombocytopenia. First, the drug was discontinued, but most of the chemotherapy drugs had myelosuppressive effects. Find a drug that does not have myelosuppressive effects instead, if possible, available molecules A drug that has a structure that is not related to the original drug and has a similar effect, instead of a drug that causes immune thrombocytopenia, infusion of a platelet suspension and fresh whole blood at the time of severe thrombocytopenia, the same treatment as drug-induced thrombocytopenia, but drug immunization Sexual thrombocytopenia can be treated with adrenocortical hormone. For cases with ineffective hormones, high-dose gamma globulin can be administered intravenously. The dose and usage are the same as above.

Secondary immune thrombocytopenic purpura prevention in children

The key to preventing the occurrence of this disease is to eliminate the cause of secondary immune thrombocytopenic purpura.

1. Rational use of drugs: Chemical substances, especially drugs, are the most common factors leading to secondary immune thrombocytopenic purpura. Therefore, it is necessary to pay attention to rational use of drugs, strictly control the application of drugs that are harmful to the hematopoietic system, and prevent abuse. The hematopoietic system has damaged drugs, and the blood is regularly observed during use.

2. Avoid damage from poisons or radioactive materials: When contacting the hematopoietic system poisons or radioactive substances, various protective measures should be strengthened. Patients should reduce the number of radiological diagnosis and treatment as much as possible to avoid excessive radiation, and regularly perform blood tests.

3. Active prevention and treatment of viral infections: vigorously carry out prevention and treatment of viral hepatitis and other viral infections. Viral infections are closely related to the pathogenesis of secondary immune thrombocytopenic purpura. The most common is hepatitis virus. Therefore, do a good job in vaccination. Strengthen physical exercise, pay attention to food hygiene, maintain a comfortable mood, work and rest, enhance the body's resistance, prevent and control the occurrence of various infections.

Secondary immune thrombocytopenic purpura complications in children Complications, intracranial hemorrhage, hematuria, acute renal failure

The disease itself can be complicated by gastrointestinal bleeding, pulmonary hemorrhage, intracranial hemorrhage, hematuria, and even acute renal failure, often causing death, other diseases vary depending on the disease.

Secondary idiopathic thrombocytopenic purpura symptoms in children Common symptoms Skin gastrointestinal tract bleeding, ecchymosis, episodes, thrombocytopenia, intracranial hemorrhage, gingival bleeding, cold, hematuria, positive beam test

The clinical symptoms depend on the degree of thrombocytopenia and the body's response. Hemorrhage occurs after decompensation of bone marrow megakaryocytes. There may be skin ecchymosis, nosebleeds, gum bleeding, etc. In severe cases, the skin of the whole body is red, followed by fever. Chronic war, severe bleeding including oral mucosal bleeding bullae, gastrointestinal bleeding, hematuria, pulmonary hemorrhage, intracranial hemorrhage, etc.; some cases of taking quinine have microvascular anemia, complicated with acute renal failure, viral infection caused by platelets Reduction, such as aplastic anemia after hepatitis, clinical manifestations of hepatitis damage, aplastic anemia in the presence of thrombocytopenia, followed by the emergence of red blood cell line and granulocyte cell proliferation, with anemia as the main performance, often appear infection, MDS In addition to megakaryocyte-induced thrombocytopenia, erythrocyte lineage, granulocyte-monocyte lineage hematopoiesis, leukemia, malignant lymphoma, cancer metastasis, etc., due to malignant tumor invasion of bone marrow, megakaryocyte production is reduced and maturation is inhibited, resulting in platelets In addition to the clinical symptoms of primary disease and bleeding, the disease with the relief of the disease Small plates can return to normal, drugs cause immune thrombocytopenia, from ingestion of drugs to causing immune thrombocytopenia, clinically there is often an incubation period, the length of this period varies, quinine and quinidine can be as short as several hours, For about 2 weeks, the indomethacin, indomethacin (indomethacin), gold salt, etc. can last for several months.

Examination of secondary immunological thrombocytopenic purpura in children

1. Blood test: The platelet count is reduced, and the weight is often <(1~10)×109/L, the bleeding time is prolonged, the blood clot is poorly contracted; the viral hepatitis has abnormal liver function test.

2. Bone marrow examination: the number of bone marrow megakaryocytes is normal or increased with maturity disorder, MDS appears megakaryocyte reduction and erythrocyte lineage, granulocyte-monocyte lineage hematopoiesis, diagnosis depends on bone marrow puncture showing one or two lines of pathological hematopoiesis In addition, stem cell culture, chromosome examination, leukemia, malignant lymphoma, cancer metastasis and other malignant tumors should be done. Invasion of the bone marrow reduces megakaryocyte production and inhibits maturation, showing thrombocytopenia.

3. Immunological examination: There are some methods for measuring antibodies in vitro, such as measuring antibodies induced by quinine, quinidine, etc., and the patient's serum or plasma, normal human platelets, and sensitizing drugs can be mixed for immunoassay. There is a clot retraction inhibition test, that is, the patient's serum inhibits the blood clot contraction of the compatible blood type in the presence of the relevant drug, indicating the presence of antibodies related to the drug, and the use of flow cytometry to determine the antibody will increase the sensitivity and stimulate the drug in vivo. The test has also been done, but it is more dangerous.

4. Beam arm test: the result is positive.

5. Regular chest X-ray, B-ultrasound examination: viral hepatitis has abnormal manifestations such as liver enlargement.

6. Other examinations: According to clinical necessity, choose other tests such as CT.

Diagnosis and differential diagnosis of secondary immune thrombocytopenic purpura in children

Diagnose based on:

1. History of suspicious drugs: history of medication in recent medical history in the past few weeks.

2. There is bleeding performance: clinically, skin and mucous membrane spontaneous bleeding is the main; beam arm test is positive.

3. Laboratory: Reduced platelet count, such as drug-related antibodies can be diagnosed drug-induced immune thrombocytopenia.

4. Bone marrow examination: megakaryocyte proliferation, maturity disorder.

5. Platelet aggregation and platelet anti-human globulin test positive.

6. Clot retraction inhibition test is positive.

7. Platelet factor-3 (PF3) is positive.

8. In vitro suspicious drugs act positive on the test platelet test.

Differential diagnosis

1. Aplastic anemia: manifested as fever, anemia, bleeding, three major symptoms, liver, spleen, lymph nodes are not large, similar to secondary immune thrombocytopenic purpura associated with anemia, but generally anemia is heavier, total white blood cells And neutrophils are reduced, reticulocytes are not high, bone marrow is red, granulocyte system is reduced in blood function, megakaryocytes are reduced or extremely difficult to find.

2. Acute leukemia: secondary immune thrombocytopenic purpura needs to be differentiated from leukemia with no increase in white blood cells. It can be confirmed by bloody smear showing various stages of immature white blood cells and bone marrow examination.

3. Allergic purpura: for symmetrical hemorrhagic plaque, the lower extremities are more common, and there are many platelets, which are generally easy to identify.

4. Lupus erythematosus: early manifestations of thrombocytopenic purpura, suspected when anti-nuclear antibodies and lupus cells (LEC) can help identify.

5. Wiskortt-Aldrich syndrome: in addition to hemorrhage and thrombocytopenia, combined with extensive eczema and easy infection, decreased platelet adhesion, no agglutination reaction to ADP, adrenaline and collagen, is a recessive hereditary disease, the incidence of male infants , died within 1 year of age.

6. Thrombotic thrombocytopenic purpura: seen at any age, the basic pathological changes are eosinophilic embolization of small arteries, previously thought to be platelet embolism, and confirmed by fibroin embolization by fluorescent antibody test, this vascular damage can occur in various organs Clinical manifestations of thrombocytopenic hemorrhage and hemolytic anemia, hepatosplenomegaly, hemolysis is more urgent, fever, and abdominal pain, nausea, diarrhea and even coma, convulsions and other neurological symptoms, reticulocyte increase, around Nuclear red blood cells appear in the blood, serum anti-human globulin test is generally negative, can show renal dysfunction, such as hematuria, proteinuria, azotemia, acidosis, serious prognosis, adrenal cortical hormone only temporary combination of mitigation.

7. Idiopathic thrombocytopenic purpura: secondary thrombocytopenic purpura can often be found in the cause, such as infection, various splenomegaly, bone marrow disease, chemical and drug allergy and poisoning, and idiopathic Thrombocytopenic purpura, regardless of medical history, clinical manifestations and laboratory tests can not find the cause.

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