| disease | Idiopathic Thrombocytopenic Purpura |
| alias | Immune Thrombocytopenic Purpura, ITP |
Idiopathic thrombocytopenic purpura (ITP) is the most common bleeding disorder in children, characterized by spontaneous bleeding, thrombocytopenia, prolonged bleeding time, and poor clot retraction. The development of megakaryocytes in the bone marrow is inhibited. According to statistics from Beijing Children's Hospital from 1955 to 1980, among 4,000 children hospitalized for bleeding disorders, 1,004 cases were thrombocytopenic purpura, accounting for 25.1%. Recent studies support the involvement of immune mechanisms in ITP, hence it is now suggested to be renamed as immune thrombocytopenic purpura.
bubble_chart Etiology
Approximately 80% of affected children have a history of viral infection about 3 weeks before the onset of the disease, mostly upper respiratory tract infections, while about 20% of patients have precursor conditions such as rubella, measles, chickenpox, mumps, infectious mononucleosis, hepatitis, or cytomegalic inclusion disease. About 1% of cases develop the disease after receiving live vaccines.
Currently, it is believed that viral infections cause ITP not through direct viral action but via immune mechanisms. This is because symptoms often appear 2–3 weeks after the infection, and most patients exhibit an increase in platelet surface-coated antibodies (PAIgG), leading to platelet destruction by phagocytes. Acute cases show higher antibody levels and more severe platelet destruction compared to chronic cases. Some patients simultaneously develop thrombocytopenic purpura and autoimmune hemolysis, while about half of neonatal cases involve mothers with the same condition. These observations support the classification of ITP as an immune-mediated disease.
bubble_chart Clinical Manifestations
This disease occurs in children of all ages and is divided into acute (≤6 months) and chronic (>6 months) types. Acute ITP is more common in infants and young children during childhood, with a significant decrease after the age of 7. The incidence is higher in spring. There is usually no prior history of bleeding, with sudden onset and severe bleeding, often preceded by or concurrent with upper respiratory tract infections. Chronic cases show no distinct age peak but are more common in school-age children, with insidious onset and milder bleeding symptoms. About 10% of patients transition from acute to chronic. The condition can also be classified into four grades: ① Grade I: platelet count <100×109/L (100,000/mm3
) but >50×109/L, bleeding only after trauma; ② Grade II: platelet count ≤50×109/L but >25×109/L, without widespread bleeding; ③ Grade III: platelet count <25×109/L but >10×109/L, with widespread bleeding and persistent bleeding at trauma sites. ④ Severe Grade III: platelet count <10×109/L, with spontaneous, life-threatening bleeding (including intracranial hemorrhage).The hallmark of ITP bleeding is widespread skin and mucous membrane bleeding, often presenting as scattered pinhead-sized intradermal or subcutaneous hemorrhages, forming petechiae or ecchymoses. These are more common on the limbs but can also appear as generalized bleeding spots or hematomas. Some patients primarily complain of severe epistaxis (accounting for about 20–30%) or gingival bleeding. Hematemesis or melena is common, mostly due to swallowing blood from oral or nasal bleeding, while true massive gastrointestinal bleeding is rare. Subconjunctival hemorrhage is also a frequent symptom. Gross hematuria is occasionally seen. About 1% of patients experience intracranial hemorrhage, which is the leading cause of death in ITP. Adolescent girls may present with hypermenorrhea. Bleeding in other areas, such as the chest, abdomen, or joints, is extremely rare.
Apart from skin and mucous membrane bleeding, only 10–20% of patients have Grade I splenomegaly. Acute onset is often accompanied by fever. Severe bleeding may lead to hemorrhagic anemia and, in some cases, hemorrhagic shock. Symptoms related to localized hematomas may occur, and intracranial hemorrhage manifests as headache, drowsiness, unconsciousness, spasms, paralysis, etc. In acute fulminant cases, in addition to thrombocytopenia, vascular wall damage is often present, resulting in more severe bleeding.
bubble_chart Auxiliary Examination
1. Blood Picture In cases with mild bleeding, there is usually no change in red or white blood cells. Occasionally, abnormal lymphocytes may be observed, suggesting a viral infection. During acute bleeding episodes or after repeated bleeding, red blood cells and hemoglobin often decrease, while white blood cells increase. Reticulocytes may rise after significant bleeding. The most notable change in peripheral blood is a reduction in platelets to below 100×109
2. Bone Marrow Picture In severe bleeding cases, reactive hematopoietic hyperactivity may be observed. In acute sexually transmitted disease cases, the total number of megakaryocytes is normal or slightly increased. In chronic sexually transmitted disease cases, megakaryocytes are often elevated, frequently exceeding 0.2×109L (200/mm3) and sometimes as high as 0.9×109L [normal range: (0.025–0.075)×109L]. Megakaryocyte classification shows normal or slightly elevated percentages of promegakaryocytes and immature megakaryocytes. Mature megakaryocytes that have not released platelets are significantly increased, accounting for up to 80%, while mature megakaryocytes that have released platelets are rare. Bone marrow examination is necessary to confirm the diagnosis and exclude leukemia or aplastic anemia.
3. Platelet Antibody Testing The primary finding is an increase in platelet surface IgG (PA IgG), with a positive rate of 66–100%. Simultaneous testing of PAIgG, PAIgM, and PAIgA can improve detection rates. Elevated PAIgG is not specific to this disease and may also occur in other immune disorders. However, non-immune thrombocytopenic purpura does not show elevated PAIgG. Monitoring PAIgG levels is clinically significant for predicting the prognosis of ITP: platelet counts typically rise only after PAIgG declines. Reports indicate that cases with PAIgG levels >1.1×10-12g per platelet do not respond to steroid therapy, whereas cases with PAIgG levels of (0.5–1.0)×10-12g per platelet show good steroid response. Extremely high PAIgG before splenectomy also predicts poor surgical outcomes. Normalization of PAIgG after steroid therapy or splenectomy indicates a favorable prognosis, while persistently elevated PAIgG suggests treatment failure.
4. Shortened Platelet Lifespan Using isotopes 51Cr or 111In to label platelets transfused into ITP patients, platelet lifespan is markedly shortened, sometimes lasting only a few hours (1–6 hours, compared to the normal 8–10 days). Isotope surface counting can also identify sites of platelet sequestration and destruction (spleen, liver, lungs, bone marrow). Platelet adhesion and aggregation tests may reveal functional abnormalities in platelets of chronic ITP patients.
The clinical presentation is mainly characterized by bleeding, without significant enlargement of the liver, spleen, or lymph nodes, with a platelet count <100×109/L. The bone marrow is dominated by nucleated cells, and the total number of megakaryocytes is increased or normal. Antiplatelet antibodies (PAIgG, M, A) are detected in the serum, and platelet lifespan is shortened. The diagnosis can be made after excluding other diseases that cause thrombocytopenia.
bubble_chart Treatment Measures
1. General Therapy: Acute sexually transmitted disease cases mainly experience heavier bleeding within 1–2 weeks of onset. Therefore, during the initial stage [first stage], activity should be reduced, and trauma, especially head injuries, should be avoided. Grade III patients should rest in bed. Active prevention and control of infection are essential, and aspirin, which can cause bleeding, should also be avoided. Provide adequate fluids and easily digestible food to avoid mucosal membrane injury. To reduce bleeding tendency, large doses of vitamins C and P are often administered. Local bleeding should be controlled by compression. Most cases do not require special treatment. However, for severe bleeding or suspected intracranial hemorrhage, active hemostatic measures should be taken. Chronic sexually transmitted disease cases with mild bleeding or in the stage of remission do not require special treatment, but trauma should be avoided, and infection should be prevented, as even minor respiratory infections can trigger severe relapses. For severe or persistent bleeding, the following special therapies should be considered.
2. Fresh Blood or Platelet Transfusion: This is only suitable as emergency treatment for severe bleeding. Since the patient’s blood contains antiplatelet antibodies, transfused blood or platelets are rapidly destroyed, with a short lifespan (minutes to hours). Therefore, transfusion does not effectively increase platelet counts. However, some believe that platelet transfusion can quickly reduce capillary fragility and alleviate bleeding tendency.
3. Adrenocortical Hormones: The therapeutic effects of hormones are generally attributed to: ① reducing capillary permeability and bleeding tendency; ② diminishing immune responses, reducing PAIgG production, and inhibiting the phagocytosis of antibody-coated platelets by splenic mononuclear macrophages. Thus, early administration of high-dose hormones in ITP patients can lead to rapid improvement in bleeding symptoms. Currently, it is recommended that patients with grade II or higher severity within the first month of onset (especially within 2 weeks) or those with prolonged disease but grade III or higher severity should receive hormone therapy. The treatment principle is early, high-dose, and short-term. Typically, prednisone 60mg/m2·d (2mg/kg·d) is administered orally in 2–3 divided doses or as a single morning dose. For severe bleeding, prednisone can be increased to 120mg/m2·d orally, or hydrocortisone 400mg/m2·d or dexamethasone 10–15mg/m2·d can be given intravenously. Once bleeding improves, switch to prednisone 60mg/m2·d. Treatment generally lasts about 3 weeks, not exceeding 4 weeks, followed by gradual tapering and discontinuation.
4. High-Dose Intravenous Immunoglobulin (IVIG): For children with severe bleeding, high-dose purified immunoglobulin (IgG) can be administered intravenously at approximately 0.4g/kg·d for 5 days. About 70–80% of patients show an increase in platelet counts, particularly in chronic cases, serving as a temporary alternative to splenectomy. However, this refined product is expensive and not easily accessible.
5. Immunosuppressants: For patients unresponsive to hormone therapy, the following may be tried: ① Vincristine 1.5–2mg/m2 (maximum dose 2mg per dose) intravenously once weekly; or 0.5–1mg/m2 diluted in 250ml of normal saline for slow intravenous infusion, administered for 4–6 weeks as one course. Platelet counts may rise during treatment, but most patients relapse after discontinuation, with only a few achieving long-term remission. Due to its transient efficacy, it is more suitable for preoperative preparation. ② Cyclophosphamide 2–3mg/kg·d orally or 300–600mg/m2 intravenously once weekly. Efficacy is usually observed within 2–6 weeks; if ineffective after 8 weeks, discontinue. Effective cases may continue for 4–6 weeks. ③ Azathioprine 1–3mg/kg·d, with effects typically noticeable after one month. These immunosuppressants can be combined with corticosteroids.
6. Other medications: In recent years, domestically and internationally, the non-virilizing synthetic androgen ethinyl hydroxyandrostenedioxazole (Danazol, DNZ) has been trialed for the treatment of refractory chronic ITP patients. The immediate effects are relatively good, but the duration of sustained effects is short. Therefore, it holds certain value for patients preparing for splenectomy who require a temporary rise in platelet counts. Its mechanism is currently believed to involve modulating the immune regulatory function of T cells, thereby reducing antibody production and decreasing the clearance of platelets by macrophages.
7. Splenectomy Therapy: The remission rate of splenectomy for chronic ITP is 70-75%. However, surgical indications should be strictly controlled, and the timing of splenectomy should be delayed as much as possible.
According to a long-term follow-up of 974 ITP cases at Beijing Children's Hospital, 78.3% of acute cases recovered within 6 months. Among those with recurrent episodes or progression to chronic cases, about one-third required no special treatment and mostly achieved spontaneous remission within 3 years. The course of chronic cases ranged from 6 months to over 10 years, with recurrent episodes occurring at intervals as short as several tens of days or as long as several years. Among the chronic cases, 72 underwent splenectomy, with 80.5% achieving recovery or improvement postoperatively. During follow-up, 15 cases (1.9%) died, including 8 confirmed deaths due to intracranial hemorrhage, 3 from massive systemic bleeding, and 2 from other hemorrhages. Platelet counts prior to death were all <50×109/L (below 50,000/mm3), with 11 cases <10×109/L. Overall, the prognosis of this disease is relatively favorable. Previous reports indicate that approximately 90% of cases in children under 10 years old, with acute onset and secondary to infection, recover within 6 months. However, timely prevention and treatment of infections, avoidance of trauma—especially prevention of intracranial hemorrhage—and early corticosteroid therapy for severe bleeding cases are essential.
Clinically, it is often necessary to differentiate from the following diseases:
(1) Aplastic anemia: Manifested by the three major symptoms of fever, anemia, and bleeding, with no enlargement of the liver, spleen, or lymph nodes, similar to idiopathic thrombocytopenic purpura accompanied by anemia. However, the anemia is generally more severe, with a decrease in total white blood cells and neutrophils, and reticulocytes are not elevated. Bone marrow shows reduced hematopoietic function in the red and granulocyte systems, and megakaryocytes are decreased or extremely difficult to detect.
(2) Acute leukemia: ITP particularly needs to be differentiated from leukemia without elevated white blood cells. The presence of immature white blood cells at various stages in blood smears and bone marrow examination can confirm the diagnosis.
(3) Allergic purpura: Symmetrical hemorrhagic papules, mostly seen in the lower limbs, with no decrease in platelets, generally easy to differentiate.
(4) Systemic lupus erythematosus: Early manifestations may include thrombocytopenic purpura. If suspected, testing for antinuclear antibodies and lupus erythematosus cells (LEC) can aid in differentiation.
(5) Wiskott-Aldrich syndrome: In addition to bleeding and thrombocytopenia, it is accompanied by widespread eczema and susceptibility to infections. Platelet adhesion is reduced, with no aggregation response to ADP, adrenaline, or collagen. It is an X-linked recessive genetic disorder, affecting male infants, with most dying within the first year of life.
(6) Evans syndrome: Characterized by the simultaneous occurrence of autoimmune thrombocytopenia and hemolytic anemia, with a positive Coombs' test. The condition is often severe, and most patients respond to hormone therapy or splenectomy.
(7) Thrombotic thrombocytopenic purpura: Can occur at any age. The basic pathological change is eosinophilic emboli in small stirred pulses, previously thought to be platelet emboli but later confirmed by fluorescent antibody testing to be fibrin emboli. Such vascular damage can occur in various organs. Clinically, it presents as thrombocytopenic bleeding and hemolytic anemia, hepatosplenomegaly. In acute cases, fever may occur, along with abdominal pain, nausea, diarrhea, and even unconsciousness, convulsions, and other neurological symptoms. Reticulocytes are increased, and nucleated red blood cells appear in peripheral blood. Serum anti-human globulin tests are generally negative. Renal dysfunction may be evident, such as hematuria, proteinuria, azotemia, and acidosis. The prognosis is severe, and adrenal corticosteroids only provide temporary relief.
(8) Secondary thrombocytopenic purpura: Severe bacterial infections and viremia can cause thrombocytopenia. Various splenomegaly diseases, bone marrow-involved diseases, chemical and drug allergies and poisoning (drugs can directly destroy platelets or inhibit their function, or combine with plasma components to form antigen complexes, which then produce antibodies, leading to allergic reactions that destroy platelets. Initial allergic reactions may include shivering, fever, headache, and vomiting), and hemolytic anemia can all be accompanied by thrombocytopenia. Careful examination is required to identify the disease cause and differentiate it from idiopathic thrombocytopenic purpura.
