1. What kind of disease is idiopathic thrombocytopenic purpura (ITP)?
A: Idiopathic thrombocytopenic purpura, also known as primary thrombocytopenic purpura, primary immune thrombocytopenic purpura, autoimmune thrombocytopenic purpura, autoimmune idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura, immune-mediated thrombocytopenia, hemorrhagic purpura, or rarely Werlhof’s disease, abbreviated as ITP or AITP or ATP. ITP is a disease of unknown origin caused by various triggers that produce anti-platelet antibodies, excessive destruction of platelets by the spleen, etc. (liver), resulting in peripheral blood thrombocytopenia that may cause bleeding. Therefore, in 2007, the International Working Group on ITP recommended the term “immune” instead of “idiopathic”. “Instead of “idiopathic”, the International Working Group on ITP recommended in 2007 to call it “Immune ThrombocytoPenia” [“Immune Thrombocytopenia (also abbreviated as ITP) ]”. It can be said that ITP is an autoimmune disease.
2. What is the incidence of ITP?
A: The annual incidence of ITP has been reported to be at least 10 per 100,000 and even as high as 125 per 100,000 (reported in Kuwait). The annual incidence of ITP in adults in the United States is 66 per 100,000 and in children is estimated to be 50 per 100,000, of which the annual incidence of new chronic refractory ITP is about 10 per 100,000. according to statistical studies in Denmark and the United Kingdom, the annual incidence of ITP in children is about 10 to 40 per 100,000. therefore, ITP is the most common type of bleeding disorder in clinical practice.
3.What are the manifestations and laboratory tests for ITP?
A: ITP is often asymptomatic, and many patients are found only after physical examination or blood tests for other diseases (at this time, the “P” in ITP can be removed and it is called idiopathic thrombocytopenia). Platelets are one of the three types of blood cells in the blood, whose main function is to stop bleeding, with a normal value of 100,000 (100×109/L) to 300,000 (300×109/L) [150,000 (150×109/L) to 450,000 (450×109/L) in Europe and the United States]. When platelets are below 100,000 (100×109/L) [150,000 (150×109/L) in Europe and the United States], it is called thrombocytopenia. However, only when platelets are reduced to a certain level, bleeding symptoms appear, which can manifest as a variety of bleeding, such as skin petechiae, petechiae, purpura, nose bleeding, gum bleeding, oral blood blisters, excessive menstruation in women, and in severe cases, even gastrointestinal bleeding and brain hemorrhage. The amount of thrombocytopenia that will lead to bleeding varies from person to person, from condition to condition, and from the presence of comorbidities such as infections.
ITP can be classified as acute or chronic, depending on the mode of onset and course of the disease. Acute type (AITP) is usually seen in children, with no gender difference in onset, rapid onset and significant bleeding symptoms, but mostly resolves on its own, with a duration of 2 months, usually no more than 6 months. The chronic type (CITP) is mostly in young and middle-aged women aged 20-40 years, with a male to female ratio of 1:3. The onset of the disease is slow and insidious, and the bleeding symptoms are mild, often with complaints of excessive menstruation, and often recurrent, and the course of the disease can extend for six months to several years, or even decades.
All ITP patients have multiple blood tests indicating thrombocytopenia; shortened platelet lifespan, normal platelet lifespan is 8-10 days (some say 7-14 days), but ITP patients only 1-3 days, or even a few minutes; bone aspiration indicates impaired development/maturation of megakaryocytes; anti-platelet antibodies can be found in the blood of 70% of patients.
4. How is the degree of thrombocytopenia in ITP graded?
A: In general, the severity of thrombocytopenia can be divided into 4 grades: mild reduction, platelets of 50,000-100,000 (50×109/L~100×109/L), generally no bleeding tendency, can be left untreated, and even discretionary minor surgery; moderate reduction, platelets of 30,000-50,000 (30×109/L~50×109/L), with bleeding tendency, can not perform Any surgery; severe reduction, platelets of 20,000~30,000 (20×109/L~30×109/L), increased bleeding tendency, but for ITP patients should also be cautious platelet transfusion; very severe reduction, platelets <10,000 (10×109/L), most patients have skin and mucous membrane bleeding symptoms, the possibility of brain bleeding and other life-threatening bleeding, if necessary, emergency platelet transfusion.
5. How is ITP diagnosed and differentially diagnosed?
A: As already mentioned, ITP is an autoimmune disease. The diagnosis is based on.
(1) Decreased platelet count on at least 2 laboratory tests, with no abnormal blood cell morphology.
(2) The spleen is generally not enlarged.
(3) Bone marrow examination: increased or normal megakaryocyte count, with maturation disorders.
(4) Special laboratory tests for the diagnosis of ITP are.
(1) Platelet membrane antigen-specific autoantibody test. MAIPA (monoclonal antibody immobilization of platelet antigen assay) method has high specificity in detecting antigen-specific autoantibodies, which can distinguish immune from non-immune thrombocytopenia and help in the diagnosis of ITP. However, the experimental method has yet to be standardized.
②Thermopoietin (TPO). can distinguish between reduced platelet production (elevated TPO levels) and increased platelet destruction (normal TPO), thus helping to differentiate ITP from atypical remitting or hypoproliferative MDS.
(iii) H. pylori testing, HIV, and HCV.
ITP is also a diagnosis of exclusion, which is the differential diagnosis of ITP, i.e., the need to exclude various causes of so-called secondary thrombocytopenia (STP) before diagnosing ITP, including drug-induced ITP (DIITP) such as heparin-induced thrombocytopenia (HIT), ionizing radiation, genetic (or congenital) thrombocytopenia, and refractory thrombocytopenia (RT, which is MDS), acute leukemia (AL), aplastic anemia (AA) early or atypical reperfusion, thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), acquired pure megakaryocytic reperfusion (sexual thrombocytopenic purpura) (acquired pure megakaryocytic aplasia (APMA) and other hematologic disorders, and infections such as epidemic hemorrhagic fever (fever, thrombocytopenia, and urine protein) and the recent frequent fever with thrombocytopenia syndrome (SFTS, also known as human granulocytic anaplasmosis (HGA, commonly known as tick disease), and other (auto)immune diseases such as systemic lupus erythematosus (SLE) and dry syndrome, non-hematologic diseases such as thyroid disease, hypersplenism in cirrhosis, and even post-transfusion purpura (PTP), pseudothrombocytopenia (false thrombocytopenia, ED). thrombocytopenia, EDTA-PTCP). In the case of neonates, neonatal alloimmune thrombocytopenia (NAITP) should also be considered.
In conclusion, there is no “gold standard” or specific diagnostic index for the diagnosis of ITP, and the diagnosis is basically exclusionary, taking into account the patient’s medical history, physical examination, multiple platelet counts (and sometimes manual counts), peripheral blood smears, platelet autoantibodies, and even bone marrow smears and biopsies to exclude other thrombocytopenic conditions The following are some examples of thrombocytopenia, such as pseudo-thrombocytopenia (mostly caused by the application of the anticoagulant EDTA during blood collection), secondary thrombocytopenia such as lupus erythematosus, anaphylaxis, dry syndrome, antiphospholipid syndrome, pharmacological thrombocytopenia (aspirin, anti-inflammatory pain, penicillin, cephalosporin, sulfonamide, rifampin, heparin, quinine, carbamazepine, phenytoin sodium), HIV infection, hypersplenism, remittance, MDS, TTP The diagnosis of ITP can only be made when there is thrombocytopenia caused by leukemia, lymphoma, myeloma, DIC, etc., and also after viral infection, chemotherapy, radiotherapy, etc. In addition, response to hormonal therapy is also an important basis to support the diagnosis of ITP. Therefore, the diagnosis of ITP should not be made after seeing a low platelet count and not finding the “real cause” for a while, without conducting the appropriate investigations, in order to avoid misdiagnosis and the use of wrong treatment. It is recommended that patients should be diagnosed and treated in a regular hospital with proper examination conditions!
6. How is ITP staged?
A: For the staging of ITP, in the past, the duration of 6 months was used as a criterion to distinguish acute from chronic ITP, but since some patients can recover within 1 year, the International ITP Working Group now proposes new staging criteria, that is, ITP can be divided into the following types, and the treatment is also different and focused, that is, individualized treatment is needed.
(1) Newly diagnosed ITP: Patients with ITP within 3 months of diagnosis.
(2) Persistent ITP: Patients with ITP with persistent thrombocytopenia 3 to 12 months after diagnosis, including those without spontaneous remission or those who cannot maintain complete remission after stopping treatment.
(3) Chronic ITP (chronic ITP, CITP): Patients with ITP whose thrombocytopenia has persisted for more than 12 months.
(4) Severe ITP (severe ITP): Patients with platelets <10×109/L who have bleeding symptoms requiring treatment at the time of consultation or new bleeding symptoms occurring during conventional treatment and requiring treatment with other platelet-elevating drugs or increasing the dose of existing treatment.
(5) Refractory ITP (refractory ITP): refers to patients who meet all three of the following conditions.
(i) Ineffective or recurrent after splenectomy.
(ii) Treatment is still required to reduce the risk of bleeding.
③Excluding other causes of thrombocytopenia, the diagnosis of ITP is confirmed.
7.How is ITP treated?
A: The goal of ITP treatment is to maintain platelets at a safe level and to minimize treatment toxicity without having to bring the patient’s platelet count to normal. The European guidelines for the diagnosis and treatment of chronic ITP recommended in the following clinical procedures blood platelet safety values are: oral examination ≥ 10 × 109 / L; tooth extraction, filling ≥ 30 × 109 / L; minor surgery ≥ 50 × 109 / L; major surgery ≥ 80 × 109 / L; normal vaginal delivery ≥ 50 × 109 / L; cesarean section ≥ 80 × 109 / L. For patients who must take aspirin, warfarin, etc. For patients who must take anticoagulants such as aspirin and warfarin, their platelet counts should be maintained at 50×109/L or higher.
Because 80% of acute type patients have a history of upper respiratory tract infection before onset or relapse, and chronic ITP patients, infection can cause aggravation of the disease, therefore, ITP patients should usually pay attention to weather changes to increase or decrease clothing to avoid colds. Those with significant bleeding should rest in bed and avoid trauma. Platelet function antagonists such as pansentin, aspirin, anti-inflammatory pain, anagrelide, clopidogrel, ticlopidine, abciximab, eptifibatide, cilostazol, and prasugrel are contraindicated. cilostazol, prasugrel, etc.
The following treatments are available for ITP.
(1) Glucocorticoids (hereafter referred to as hormones): are the first choice of treatment drugs for ITP. Prednisone tablets usually start at 1 mg/kg/d, or methylprednisolone tablets can be applied in an equivalent conversion method. For more severe bleeding, dexamethasone or methylprednisolone may be used for a short period of time. The platelets generally rise in 7~10 days of application and reach the peak value in 2~4 weeks. After the platelets stabilize (rise to normal or near normal), the hormone dosage can be gradually reduced and the treatment can be maintained for 3~6 months or longer with small dose of prednisone (5~10mg/d) or equivalent amount of methylprednisolone. The efficiency rate is higher than 80% for the first treatment with short duration of disease. If the patient’s platelets are still not elevated after 4-6 weeks of hormone therapy, this indicates that prednisone therapy is ineffective and should be rapidly reduced to discontinuation in favor of other treatments. In clinical practice, three conditions are often encountered that lead to inadequate treatment: First, the hormone is reduced too quickly, starting to reduce the dose when the platelets are not yet stable, or reducing the dose too quickly after stabilization. Secondly, the drug is stopped too early without maintenance therapy. Third, the hormone dosage is insufficient, including the starting dose and maintenance dose, mainly because of the many side effects after long-term application. The importance of adequate initial treatment (hormone dosage can be calculated based on body weight), appropriate and individualized dosage reduction, and longer maintenance treatment (see above for the amount of hormone for maintenance treatment) should be emphasized in clinical treatment. Patients should also be educated to use the medication according to medical prescriptions and not to stop the medication on their own and give up the previous work, nor to reduce the hormone dosage on their own and affect the efficacy.
(2) High-dose intravenous gammaglobulin for.
(1) Critical ITP with significant and life-threatening bleeding, especially acute ITP in children.
(ii) Refractory ITP (RITP).
③ ITP that should not be treated with hormone therapy such as pregnant women, diabetes, ulcer disease, hypertension, tuberculosis, etc.
④Patients with ITP who need rapid platelet boosting, such as emergency surgery, delivery, etc. The dose is 0,4g/kg/d×5d or 1,0g/kg/d×2d.
(3) Splenectomy: 1/3 of platelets are stored/withheld in the spleen under normal physiological conditions, and the spleen of ITP patients is the main site for the production of platelet antibodies and destruction of platelets. It is believed (Western medical view) that spleen excision is the only means to cure ITP at present. For.
① those for whom hormonal treatment for 3-6 months (some say >6 months) is ineffective.
(ii) Those who are effective with hormone therapy but need a larger amount of maintenance such as >30mg/d.
③ those who have contraindication to use hormone, etc., splenectomy can be considered with an efficiency rate of 70%~90%. The bleeding stops rapidly after surgery and the platelet count rises rapidly immediately after splenectomy in short cases (even before the operator closes the abdominal cavity), and also in long cases in a few days. Only a small percentage of patients are initially effective after splenectomy and then relapse, but even this group of patients has increased responsiveness to other treatments, e.g. the need for glucocorticoids may be reduced. It is best to consider this procedure only in children over 10 years of age because of the possibility of outbreak of pulmonary infection (OPSI) or sepsis (PSS) after splenectomy. Because OPSI/PSS is uncommon but fatal, especially within 2 years after splenectomy, immunization against encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae infection is recommended abroad before surgery and also after splenectomy.
(4) Immunosuppressive therapy: such as vincristine, cyclophosphamide, azathioprine, cyclosporine A, mycophenolate (primaquine), etc., mainly used for the treatment of RITP.
(5) Application of general hemostatic drugs: e.g., Aniloxin, Hemostatin, Lithopodium, etc.
(6) Others: Western drugs such as danazol, plasma exchange, alpha interferon (IFN-α), high-dose vitamin C, anti-CD20 monoclonal antibodies (rituximab, melphalan) and TPO and its receptor agonists, etc. In addition to classical glucocorticoid therapy, high doses of gammaglobulin, cyclosporine A, IFN-α, rituximab and primaquine, the following experimental treatments are currently available for RITP: anti-Rh(D) immunoglobulin, Antova, MDX-33, Campath-1H (alemtuzumab), immunosorbent and H. pylori (Hp) clearance. .
(7) Chinese medicine discriminatory treatment.
It should be noted that single-collection platelet transfusion is generally not advocated because of the production of homozygous allogeneic platelet antibodies. Therefore, the indications should be strictly controlled, except for critical bleeding and before surgery, and only as a last resort, and it is best to transfuse single donor platelets (SDP) matched by HLA matching.
ITP is an autoimmune, benign disease for which there is no cure, and the goal of ITP treatment is to raise the platelet count to a safe range to prevent severe bleeding and reduce mortality, not to bring the platelet count to a normal range. Therefore, in clinical practice, if the platelet count is greater than 30×109/L, there is no bleeding, and the patient is not engaged in work or activities that increase the risk of bleeding, the patient may not be treated, but should be followed up and observed. If the platelets are lower than 30×109/L, or if there are bleeding symptoms, or if the patient is older, has been ill for a long time, or has coagulation disorders, platelet function defects, or has hypertension, infection, trauma, or is taking anti-platelet aggregation drugs, then therapeutic intervention is required. For patients who do not require therapeutic intervention, overtreatment can increase the incidence of complications such as infections, which can be life-threatening in severe cases. For patients who need treatment, it is also necessary to take into account the risk of bleeding, efficacy, side effects and patient compliance, and to weigh the pros and cons and use appropriate individualized treatment to minimize drug side effects without compromising efficacy.
8. What is the prognosis of ITP?
A: ITP is not a malignant disease, except for a very small number of life-threatening bleeding due to platelets below 10,000 (10×109/L), the prognosis is generally good. Acute forms, especially in children, will spontaneously resolve in 80% of cases. Chronic type (especially refractory) patients have recurrent episodes and a long course of disease, but most of them can be cured after a combination of Chinese and Western medicine, spleen cutting and other comprehensive treatment.