Neonatal thrombocytopenic purpura

Introduction to neonatal thrombocytopenic purpura Neonatal thrombocytopenic purpura is very common in clinical practice. Thrombocytopenia is one of the main causes of neonatal hemorrhage. The normal range of platelet counts in neonates and premature infants is similar to that of other age children. It is generally believed that the platelet count <100×109/L (100,000/mm3) is thrombocytopenia, and some people think that less than 150×109/L (150,000/mm3) is abnormal, and the cause should be identified. There are many causes of thrombocytopenic purpura in neonates, and the pathogenesis is complicated and the clinical manifestations are diverse. basic knowledge Probability ratio: Susceptible people: children Mode of infection: non-infectious Complications: Infectious thrombocytopenic purpura

Neonatal thrombocytopenic purpura

(1) Causes of the disease

The blood platelet level is the result of balance between platelet production and destruction. Therefore, there are three reasons for neonatal thrombocytopenia, megakaryocyte production or release of thrombocytopenia, increased platelet destruction, or both. Classification according to the etiology and pathogenesis, neonatal thrombocytopenia can be divided into immune, infectious, congenital or hereditary, etc., the main types of neonatal thrombocytopenic purpura are now described below.

Immune thrombocytopenic purpura

(1) Immune thrombocytopenic purpura: In the case of maternal and fetal platelet antigenicity, the platelet count is often less than 30×109/L when the baby is born, so bleeding occurs.

(2) Congenital passive immune thrombocytopenic purpura: This disease is characterized by antibodies that damage both mother's platelets and fetal platelets. According to the etiology, they can be divided into the following two categories:

1 maternal idiopathic thrombocytopenic purpura: women with active idiopathic thrombocytopenic purpura, such as pregnancy, blood anti-platelet antibodies can enter the fetal blood circulation through the placenta to destroy fetal platelets, resulting in thrombocytopenia.

2 maternal systemic lupus erythematosus: anti-platelet antibodies in the blood can enter the fetus through the placenta, after the baby is born, more common thrombocytopenia.

(3) Neonatal hemolytic disease with thrombocytopenia: severe neonatal hemolysis often has thrombocytopenia.

(4) drug-induced thrombocytopenic purpura: drug-induced neonatal thrombocytopenia, can be divided into congenital and acquired two:

1 congenital: pregnant mothers used a certain drug in the second trimester to be sensitized, when the same drug is used, a large number of antibodies are produced to destroy fetal platelets, the main drugs are sulfonamide, quinine, quinidine, p-aminosalicylic acid , phenobarbital, chlorothiazide and the like.

2 acquired nature: after birth, newborns use certain drugs, such as sulfonamide, digoxin, indomethacin, etc., to produce anti-platelet antibodies and destroy platelets.

2. Infectious thrombocytopenic purpura: Infectious thrombocytopenic purpura is common in a variety of viruses, bacteria, spirochetes (syphilis) and protozoal infections, or DIC due to severe infections, including intrauterine infections and postnatal infections, especially The former is easy to combine with thrombocytopenia.

(1) intrauterine infection: mostly congenital chronic infection, common pathogens include toxoplasma, rubella, cytomegalovirus, human herpesvirus (collectively called TORCH), coxsackie virus, measles and hepatitis virus, among which giant cells Viruses and rubella viruses are the most common.

(2) Postnatal infection: infection after birth is mainly caused by bacterial infection, mainly Staphylococcus aureus and Gram-negative bacilli infection, such as sepsis, purulent meningitis, pneumonia, enteritis, umbilical inflammation, urinary tract infection, etc. , often secondary to thrombocytopenia.

3. Congenital or hereditary thrombocytopenic purpura

(1) Congenital megakaryocyte hyperplasia: decreased or absent bone marrow megakaryocytes, leading to thrombocytopenia, may be simple congenital hyperplasia, thrombocytopenia, may also be associated with various congenital malformations, the cause of the disease is unknown, may be associated with pregnant women It is related to taking drugs or infections, and others think it is related to heredity.

(2) hereditary thrombocytopenic purpura: several hereditary thrombocytopenia syndromes have been reported in the literature, among which Wiskott-Aldrich syndrome is a kind of X-linked recessive genetic disease. The etiology is still unclear. It is thought to be associated with allergies, mononuclear-macrophage system hyperplasia, and chronic infection. In recent years, it has been considered that thrombocytopenia is caused by defects in platelets itself. This disease has a family history, female transmission, and male onset.

(two) pathogenesis

1. Immunological thrombocytopenic purpura is a group of diseases caused by immune-induced thrombocytopenia.

(1) Immune thrombocytopenic purpura: the pathogenesis is caused by the antigenicity of platelets in mother and child. It is characterized by the presence of anti-platelet antigen immune antibodies in both mother and fetal blood. The antibody is IgG and can enter the fetus through the placenta. In vivo, covering the fetal platelets, thereby accelerating the destruction of platelets, causing the baby to reduce thrombus after birth, such as antibodies only destroy fetal platelets, said the same family of immune thrombocytopenia, such as antibodies simultaneously destroy the mother and fetal platelets, said autoimmune or Congenital passive immune thrombocytopenia, if the fetus has PIA1 antigen (obtained from the father) and the mother lacks this antigen, the mother can be sensitized by pregnancy or has received blood with PIA1 antigen, producing antibodies against PIA1 antigen. It can enter the fetal blood circulation through the placenta, causing the fetal platelet destruction to accelerate, and the life of the platelets is thus significantly shortened. When the baby is born, the platelet count is often less than 30×109/L (30,000/mm3) and bleeding occurs.

(2) congenital passive immune thrombocytopenic purpura: a woman with active idiopathic thrombocytopenic purpura, such as pregnancy, the blood anti-platelet antibodies can enter the fetal blood circulation through the placenta to destroy fetal platelets, the birth of the baby can occur Thrombocytopenic purpura, such as pregnant women after spleen, due to other mononuclear-macrophage system can still produce antibodies, these antibodies for pregnant women because of no spleen and harmless, maternal platelet count is normal, but this antibody enters the fetus through the placenta, Because the spleen of the fetus has a normal function, it can destroy the platelets and cause thrombocytopenia. For the mother patient with systemic lupus erythematosus, the anti-platelet antibody in the blood enters the fetus through the placenta and reaches the baby.

(3) Neonatal hemolytic disease with thrombocytopenia: due to the presence of both red blood cells and platelet homologous immune antibodies, red blood cells and platelets are destroyed at the same time; or a large number of red blood cells are destroyed, releasing erythropoietin, which acts similarly to platelet factor III It can accelerate the blood coagulation process, increase the consumption of platelets, and reduce the thrombocytopenia. If the blood transfusion is used for blood transfusion, thrombocytopenia often occurs after several days of blood transfusion.

(4) Congenital drug-induced thrombocytopenic purpura: The pregnant mother is mostly allergic, and is sensitized after using a certain drug in the third trimester. When the same drug is used, a large amount of antibody is produced into the fetus, which will damage the fetal platelet.

When this happens, there are three factors at the same time: platelets, antibodies and drugs, antibodies (an Ig G) and drugs can enter the fetus through the placenta, destroying fetal platelets, causing thrombocytopenic purpura after birth, purpura It can disappear within a few days, but immune antibodies in the baby's blood can exist for several months.

(5) Acquired drug-induced thrombocytopenic purpura: It is a neonatal application of certain drugs that can cause immune thrombocytopenia, such as sulfonamide, phenytoin, quinine, quinidine, digoxin (immunized antibody is IgG), chlorine Thiazide, indomethacin (immunized antibody is IgM), rifampicin (immunized antibodies are IgM and IgG), and some of them can cause toxic thrombocytopenia.

2. Infectious thrombocytopenic purpura: When the pregnant mother is infected with toxoplasma, syphilis, cytomegalovirus, rubella, herpes virus, etc., during the last 3 months of pregnancy, these pathogens can enter the fetal blood circulation through the placenta and become thrombocytopenic. The mechanism is complex, probably due to the proliferation of the virus in megakaryocytes, affecting platelet production, inhibition of bone marrow, production of anti-platelet antibodies, swelling of the spleen and increased platelet destruction, or excessive platelet consumption due to concurrent DIC (at this time Associated with other clotting factor defects, the mechanism of infection leading to thrombocytopenia is complex, infection can produce platelet antibodies, inhibit bone marrow production of platelets, toxin destruction.

3. Congenital or hereditary thrombocytopenic purpura: Congenital megakaryocyte hyperplasia is caused by decreased or absent bone marrow megakaryocytes, leading to thrombocytopenia, hereditary thrombocytopenic purpura, thrombocytopenia and hereditary defects, due to platelets Destroyed by itself, such as Wiskott-Aldrich syndrome, is a concomitant recessive genetic disease.

Neonatal thrombocytopenic purpura prevention

1. Avoid using certain drugs: Avoid using certain drugs that cause clotting, such as aspirin, indomethacin, dipyridamole, prostaglandin E1, etc., when the newborn has unexplained thrombocytopenic purpura. Stop drugs that may cause thrombocytopenia and speed up their excretion.

2. Injection of vitamin K: If the mother has a history of taking the above drugs during pregnancy, the pregnant mother should be injected with vitamin K in the late pregnancy. In addition to the injection of vitamin K after the birth, the baby should be closely observed for bleeding.

3. Etiology treatment: Etiological treatment is very important for acquired bleeding. For example, in the treatment of DIC, active control of infection, improvement of oxygen supply, correction of acidosis and electrolyte imbalance, maintenance of body temperature, etc., all help to stop the development of DIC.

Neonatal thrombocytopenic purpura complications Complications , thrombocytopenic purpura

Intracranial hemorrhage, combined with infection, severe bleeding, can cause death. Intrauterine infective thrombocytopenic purpura and congenital megakaryocyte hyperplasia and Wiskott-Aldrich syndrome, often smaller than gestational age, and have various congenital malformations, such as skeletal malformations, cardiac malformations, microcephaly, or 13 - Three-body, 18-trisomy syndrome children.

Neonatal thrombocytopenic purpura symptoms Common symptoms Urinary bilirubin negative skin mucosal bleeding ecchymosis erythrocytic thrombocytopenia jaundice nasal bleeding dyspnea convulsions

Due to different causes, the time and severity of symptoms vary.

1. Immune thrombocytopenic purpura

(1) Onset after birth: The first child can be ill after birth, and the fetus is rarely ill. Although the fetal thrombocytopenia, there is no obvious bleeding at birth, but there are defects in the minutes or hours after birth, and Infants are affected by mechanical effects during childbirth.

(2) skin bleeding: one to several hours after birth, the body's skin can quickly appear extensive bleeding points, ecchymosis, hematoma, especially in the skeletal protrusion or compression site.

(3) visceral hemorrhage: visceral hemorrhage occurs in severe cases, hemorrhage can occur in gastrointestinal bleeding, other hematuria, umbilical stump bleeding, acupuncture hole oozing or larger head hematoma, intracranial hemorrhage, etc., children with intracranial hemorrhage may appear Convulsions, difficulty breathing, cyanosis, etc.

(4) Other manifestations and outcomes: In addition to thrombocytopenia, neonates are prone to bleeding, other normal, generally no hepatosplenomegaly, hemolytic anemia, no intrauterine growth retardation or other systemic diseases, the disease is self-limiting Sexual disease, as the antibody from the mother gradually decreases and disappears, the condition recovers on its own, and the bleeding is improved after a few days, but if the amount of bleeding is large or there is intracranial hemorrhage, it will quickly turn to weight, often accompanied by heavier jaundice, the course of the disease 2 weeks to 2 months, severe cases often combined with intracranial hemorrhage, is the main cause of death.

2. Congenital passive immune thrombocytopenic purpura: clinical manifestations similar to the same family immune thrombocytopenic purpura, bleeding can occur soon after birth, mild cases can be delayed until 3 weeks after birth, common skin and mucous membrane defects , ecchymosis and purpura, or with epistaxis, gastrointestinal bleeding, hematuria, and even intracranial hemorrhage, etc., there are bleeding tendency in platelets more than 50 × 109 / L (50,000 / mm3), the duration of thrombocytopenia Long, an average of 1 month, individual delay to 4 to 6 months, due to more antibodies into the fetus.

After the birth of a mother with systemic lupus erythematosus, thrombocytopenia is common, but there is little bleeding. Sometimes there is a rash. The rash can disappear after several months. The course of disease is 4 to 8 weeks, but the bleeding is reduced after the first week.

3. Neonatal hemolytic disease with thrombocytopenia: due to the destruction of red blood cells and platelets at the same time, there are bleeding manifestations and various manifestations of hemolytic disease; if blood transfusion is used for blood transfusion, thrombocytopenia often occurs after several days of blood transfusion.

4. Drug-induced thrombocytopenic purpura: If the neonatal thrombocytopenic purpura is caused by drugs, the bleeding will be reduced and stopped after several days of withdrawal, and the platelets will gradually become normal, with a course of about 2 to 3 weeks.

5. Infectious thrombocytopenic purpura: Infants with intrauterine infection are often small for gestational age, often with congenital malformations, hepatosplenomegaly and jaundice caused by hemolysis and hepatitis, often appear bleeding hours after birth, purpura Often manifested as a wide range of blue-violet ecchymosis, about 1 week to resolve. But thrombocytopenia can be extended to a few weeks to return to normal, bleeding or bleeding and the degree of bleeding associated with platelet count, such as <30 × 109 / L (30,000 / Mm3) has a poor prognosis and can even die from pulmonary hemorrhage or massive gastrointestinal bleeding.

6. Congenital megakaryocyte hyperplasia: infants are often small for gestational age, such as microcephaly, 13-trisomy or 18-trisomy syndrome, in which thrombocytopenia-free tibial (TAR) syndrome is a representative There are obvious skeletal deformities, the most prominent in the absence of the humerus, and other limb abnormalities, such as short limb deformity, lack of arms and legs, lack of ulna, etc., 1/3 have congenital heart disease, about half have leukemia Response, white blood cell count exceeded 40 × 109 / L (40,000 / mm3), thrombocytopenia and hemorrhage vary, bone marrow puncture examination of megakaryocytes can be seen reduced or absent, about two-thirds of cases died in the first year after birth, If you can live to more than 1 year old, it is possible to gradually improve.

7. Wiskott-Aldrich syndrome, associated with hereditary defects, is destroyed by defects in the platelets themselves.

(1) Family history: There is a family history, female transmission, male onset.

(2) Clinical features: symptoms at birth or shortly after birth, thrombocytopenia and hemorrhage, eczema and complex immune deficiency, bleeding manifested as peripheral bleeding or ecchymosis, sometimes nosebleeds, ear blood, hematuria, blackening Or the outflow of blood from the anus, the prognosis of this disease is worse than more than a few months or years after birth due to concurrent infection, severe bleeding or malignant lymphoma death, but some people believe that if it can strengthen infection prevention, improve resistance, it is possible to prolong life .

(3) immunodeficiency: due to immunodeficiency often associated with infection, such as otitis media, pneumonia, meningitis and so on.

(4) Laboratory examination: platelets are continuously reduced, which can be less than 30×10 ⁹ /L (30,000/mm ³ ). The bone marrow cells are normal or increased, and can produce platelets. However, the ultrastructure of platelets is seriously disordered.

Clinically, due to the hemorrhagic disease caused by thrombocytopenia, the cause is complicated, and the cause diagnosis should be further clarified.

Examination of neonatal thrombocytopenic purpura

1. Peripheral blood: platelet count <100×10 ⁹ /L (100,000/mm ³ ) is thrombocytopenia. It is also considered that less than 150×10 ⁹ /L (150,000/mm ³ ) is abnormal, and the thrombocytopenia is light and heavy. Different, the same family of immune thrombocytopenic purpura, the baby's platelet count at birth is often less than 30 × 10 ⁹ / L (30,000 / mm ³ ), or even less than 10 × 10 ⁹ / L (10,000 / mm ³ ), after birth In children with infectious thrombocytopenic purpura, there is infectious blood, white blood cell count is significantly increased, about half of children with congenital megakaryocyte hyperplasia have leukemia-like reaction, and the number of white blood cells exceeds 40×10 ⁹ /L (40,000/mm ³ ) .

2. Cord blood: Platelets can also be found to decrease.

3. Bone marrow: The number of megakaryocytes in the bone marrow is normal when the immune thrombocytopenia is normal, while the number of megakaryocytes is reduced due to bone marrow damage, the hereditary thrombocytopenic purpura, the bone marrow cells are normal or increased, and platelets can be produced, but the ultrastructure of platelets Severe disorder, children with congenital megakaryocyte hyperplasia, bone marrow puncture examination of megakaryocytes can be seen reduced or absent.

4. Antibody detection

(1) Anti-platelet antibody: Anti-platelet antibody detection in serum, drug-induced thrombocytopenia can be examined by the following methods:

1 The serum (including antibody) of the child, the corresponding drug and the platelet of the child are added, and the platelets are agglomerated or dissolved.

2 The blood clot contraction inhibition test, that is, the serum of the child plus the corresponding drug can inhibit the blood clot contraction of the blood type, and the positive indicates that the anti-platelet antibody exists in the serum of the child.

(2) Homologous immune thrombocytopenic purpura, complement fixation test, platelet antibodies in infant blood and immune responses to father's platelets, but not in response to maternal platelets.

(3) IgG, IgM detection: When the pregnant mother is infected with toxoplasma, syphilis, cytomegalovirus, rubella, herpes virus, etc., the corresponding antibodies can be detected in the blood.

5. Coombs test: generally negative, infectious thrombocytopenic purpura Coombs test can be positive, neonatal hemolytic disease with thrombocytopenia, Coombs test positive.

6. Chromosome examination: When there are congenital malformations such as microcephaly, 13-trisomy or 18-trisomy syndrome, the chromosome can be diagnosed.

7. X-ray inspection

(1) X-ray examination of the bone: Infants with congenital megakaryocyte hyperplasia often have obvious skeletal deformities. The lack of humerus is most prominent, and other limb abnormalities such as short limb deformity, lack of arms and legs, lack of ulna, etc. .

(2) X-ray examination: 1/3 of infants with congenital megakaryocyte hyperplasia have congenital heart disease.

8. B ultrasound: may have hepatosplenomegaly, intracranial hemorrhage and other performance.

9. CT examination: the location, extent, and prognosis of intracranial hemorrhage can be determined.

Diagnosis and diagnosis of neonatal thrombocytopenic purpura

diagnosis

1. Diagnosis of immune thrombocytopenic purpura: Direct measurement of platelet antigens and antibodies in maternal and child blood can help diagnose homologous immune thrombocytopenic purpura, but the measurement technique is difficult and can only be carried out in a few scientific research laboratories. For clinical diagnosis, please refer to the following points:

(1) Congenital thrombocytopenia.

(2) Bleeding occurs shortly after birth.

(3) The mother has a normal platelet count and no bleeding tendency, no history of idiopathic thrombocytopenic purpura or taking drugs that cause immune thrombocytopenia.

(4) The baby has no history of other diseases that can cause thrombocytopenia such as infection and medication.

(5) In the complement fixation test, platelet antibodies in the baby's blood react with the father's platelets, but not with the mother's platelets.

(6) The Coombs test is generally negative.

2. Congenital immunological thrombocytopenic purpura diagnosis: clinical manifestations in addition to thrombocytopenic purpura, there is a history of systemic lupus erythematosus in infant mothers, children with rashes in addition to bleeding, rash can disappear after several months, enter the fetal antibodies More, thrombocytopenia lasts longer, the course of disease is 1 month on average, and the individual is extended to 4 to 6 months.

3. Drug-induced thrombocytopenic purpura: a history of useful medications in the mother or a child after birth (see the drug mentioned above), bleeding stopped after a few days of stopping the drug, and the platelets are gradually normal to help diagnose.

4. Infectious thrombocytopenic purpura: with intrauterine infection or postnatal infection history, and various infection manifestations, infants with intrauterine infection often have congenital malformations, hepatosplenomegaly and hemorrhage and hepatitis caused by jaundice, cyanosis often It is characterized by a wide range of blue-purple ecchymoses, which resolves in about 1 week. However, thrombocytopenia can be delayed until several weeks before returning to normal. Laboratory tests for specific antibodies such as IgG and IgM are helpful for diagnosis.

5. Congenital megakaryocyte hyperplasia: obvious skeletal malformation, the most prominent lack of tibia, congenital heart disease, often leukemia-like reactions, bone marrow puncture examination of megakaryocytes can be reduced or absent, or 13- Children with trisomy or trisomy syndrome.

6. Wiskott-Aldrich syndrome: it is destroyed due to defects in platelets itself, with a family history, boy onset, in addition to thrombocytopenia and hemorrhage, as well as the characteristics of eczema and complex immunodeficiency, often complicated by various infections, Severe bleeding or malignant lymphoma, the above characteristics can help clinical diagnosis.

Differential diagnosis

This disease is caused by thrombocytopenia or dysfunction, and should be differentiated from other common neonatal hemorrhagic diseases, such as:

1. vascular wall dysfunctional bleeding premature infants and low birth weight infants (especially very low birth weight infants) vascular wall connective tissue support weak, increased vascular fragility, injury, compression, acidosis, hypoxemia, high carbonic acid Bleeding can cause bleeding, and there is no thrombocytopenia in laboratory tests.

2. Coagulation factor deficiency or anticoagulant enhanced bleeding

(1) Disease: congenital coagulopathy such as hemophilia, congenital low (no) fibrinogenemia, K-dependent factor deficiency, hypoprothrombinemia; acquired coagulopathy such as biliary atresia or liver disease Prothrombin deficiency, secondary hypofibrinogenemia (diffuse intravascular coagulation).

(2) Identification points: The diagnosis of neonatal bleeding disorders should pay attention to the following points:

1 history and physical examination: including family history of bleeding (at least 3 generations), history of mother (infection, idiopathic thrombocytopenic purpura, lupus erythematosus), history of maternal bleeding, maternal and neonatal medication history Convulsions, anticoagulants, aspirin, etc.), whether vitamin K has been used after birth, spontaneous recurrent bleeding after birth, the health or illness of the baby when bleeding occurs, the time of bleeding, the location , degree and type, characteristics of purpura, etc., all of the above have a certain significance for diagnosis and differential diagnosis, such as neonatal hemorrhagic disease occurs 2 to 3 days after birth, generally good; hemophilia is more common skin congestion Spot, muscle and joint hematoma, and thrombocytopenic purpura more common sputum or small ecchymosis, nosebleeds, gingival bleeding and mucosal bleeding.

2 laboratory tests: the most important are 3 tests: platelet count, prothrombin time (PT) and partial thromboplastin time (PTT), such as thrombocytopenia is very diagnostic value, can further identify the cause, is immune Spontaneous thrombocytopenia, or due to infection, DIC-induced platelet destruction increases, PT is the test of the exogenous coagulation system, PTT is the determination of the endogenous coagulation system, other tests are:

A. Blood film observation: If there is red blood cell deformation or debris, it is suspected that DIC.

B. Bleeding time: The length of bleeding is related to the number and quality of platelets, capillary conditions, and poor specificity.

C. Clotting time (test tube method): It can be understood that blood hypercoagulability or hypocoagulability has a certain significance for the diagnosis and guiding treatment of DIC.

D. Determination of fibrinogen and fibrin degradation products (FDP): contribute to the diagnosis and differential diagnosis of DIC and congenital fibrinosis (the latter cannot detect FDP).

E. Whole blood clot lysis time and euglobulin partial dissolution time: used to determine plasmin activity.

F. Plasma protamine paracoagulation (3P) test: an indirect measurement of FDP.

Clinically, the first screening tests include platelet count, bleeding time, kaolin partial thromboplastin time (KPTT) and clotting time (CT). If coagulation defects are considered, further thrombin time (TT) can be performed. The latter Coagulation defect screening test with KPTT and PT.

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