Immune thrombocytopenic purpura (ITP) is a bleeding disorder with immune destruction of platelets and reduced platelets in the peripheral blood. It is characterized by extensive skin mucosal or visceral bleeding, thrombocytopenia, impaired maturation of bone marrow megakaryocytes, shortened platelet survival time and the appearance of anti-platelet autoantibodies .
I. Etiology and pathogenesis.
1, infection: bacterial or viral infection, and the development of immune thrombocytopenic purpura has a close relationship.
2, immune factors: infection can not directly lead to the development of immune thrombocytopenic purpura, the involvement of immune factors may be an important cause of the development of ITP.
3, the role of liver and spleen: in vitro culture confirmed that the spleen is the site of PAIg production in patients with immune thrombocytopenic purpura; platelets bound to PAIg or IC have altered surface properties and are easily retained in the splenic sinusoids when passing through the spleen, increasing the retention time of platelets in the spleen and the possibility of phagocytosis and clearance by the monocyte-macrophage system. The liver has a role similar to that of the spleen in platelet destruction.
4, Genetic factors: The fact that HLA–DRW and HLA-DQW positivity are closely associated with immune thrombocytopenic purpura suggests that the occurrence of immune thrombocytopenic purpura may be genetically regulated.
5, Given that immune thrombocytopenic purpura is more common in women and mostly occurs before the age of 40, it is speculated that the onset of this disease may be related to estrogen.
Second, the clinical manifestations.
1, acute type: more than half of them occur in children. Most often seen in infants and children time, after 7 years of age significantly reduced. No previous history of bleeding. more than 80% have a history of upper respiratory tract and other infections, especially viral infections, 1-2 weeks before the onset of the disease. The onset of the disease is rapid, and some patients may have chills, chills, fever, generalized skin petechiae, purpura, petechiae, and may have blood blisters and hematoma formation. Bleeding from the nose, gums, oral mucosa and tongue is common, and the injury and injection site may bleed more than once or form large petechiae. When platelets are lower than 20×10E9/L, there may be internal bleeding, such as vomiting blood, black feces, hemoptysis, urine blood, vaginal bleeding, etc. Intracranial bleeding may cause impaired consciousness, paralysis and convulsions, and is the main cause of death.
2, chronic type: mainly seen in young women under 40 years old, the onset of the disease is insidious. Generally, there are no prodromal symptoms, and it is difficult to determine the time of onset, mostly skin and mucous membrane bleeding, such as petechiae, petechiae, and trauma to stop bleeding, nasal bleeding, gum bleeding is also very common. Severe visceral bleeding is rare, but excessive menstruation is very common, and in some patients it may be the only clinical symptom, and in some patients the disease may be suddenly aggravated by infection, resulting in extensive severe visceral bleeding. Some patients with prolonged menorrhagia may develop hemorrhagic anemia, and some patients with the disease lasting for more than six months may have mild brand enlargement.
Third, laboratory tests.
1. Platelets.
(1), acute type platelets are mostly below 20×109/L, chronic type is often around 50×109/L.
(2) The average volume of platelets is large, and large platelets are easily seen.
(3) Prolonged bleeding time and poor clot shrinkage.
(4) The function of platelets is generally normal.
2.Bone marrow picture.
(1) The number of megakaryocytes is mildly increased or normal in acute type of bone marrow; the number of megakaryocytes is significantly increased in chronic type of bone marrow image.
(2) The maturation of megakaryocytes is impaired, especially in the acute type, which is characterized by small size of megakaryocytes, reduction of intracytoplasmic granules and increase of infantile megakaryocytes.
(3) Significantly fewer megakaryocytes with platelet formation (<30%).
Platelet-associated antibodies (PAIg) and platelet-associated complement (PAC): More than 80% of patients with immune thrombocytopenic purpura are positive for PAIg and PAC3, and the main antibody component is IgG or IgM, occasionally more than two antibodies are present at the same time.
4. Hemorrhagic coagulation examination.
(1), prolonged bleeding time, poor clot contraction.
(2) Positive bundle arm test.
(3) Platelet function is generally normal.
(4) Normal prothrombin time and clotting time.
(5), platelet survival time is shortened, more than 90% of patients have significantly shortened platelet survival time.
(5) Other: there may be varying degrees of normocytic or microcytic hypochromic anemia. In a few cases, evidence of hemolysis may be found (Evans syndrome).
IV. Diagnosis.
(1), extensive bleeding involving the skin mucosa and viscera, with reduced platelet count on multiple examinations.
(2), The spleen is not large or mildly enlarged.
(3), bone marrow megakaryocytosis or normal with impaired maturation.
(4), Have any of the following five items: (1) Prednisone treatment is effective; (2) Splenectomy treatment is effective; (3) PAIg positive; (4) PAC3 positive; (5) Shortened platelet survival time.
(5), exclude secondary thrombocytopenia.
V. Treatment.
1.General treatment: those with severe bleeding should pay attention to rest, and those with platelets below 20×109/L should be strictly bedridden, avoid trauma, and pay attention to the application of hemostatic drugs and local hemostasis.
2, glucocorticoids: the general situation is the first choice of treatment recent efficiency is about 80%. Commonly used is prednisone, 1-2mg/kg?d, divided or tonics. In severe cases, dexamethasone or methylprednisolone is used intravenously, and after improvement, oral prednisone is used instead. Most patients stop bleeding after a few days of medication, platelets rise in about 2 weeks, and the dose is gradually reduced (5mg per week) after platelets rise to normal or near normal, and finally 5-10mg/d maintenance treatment for 3-6 months.
3.Splenectomy: The efficiency of splenectomy treatment is about 70%-90%, and the need for glucocorticoids can be reduced for those who are ineffective. In recent years, some scholars have replaced splenectomy with splenic artery embolization, which also has good effect. It is suitable for: (1) those who have not been treated with regular glucocorticoids for 3-6 months. (2) Those who are effectively treated with hormone therapy, but relapse after reduction or discontinuation, or those who need higher dose of hormone maintenance. ③There are contraindications to the use of glucocorticoids. ④There is platelet destruction mainly in the spleen. ⑤ Those who have the tendency of intracranial bleeding and the conservative medical treatment is ineffective. Contraindications: ① Age less than 2 years (uncontrollable infection can occur after splenectomy in children under 2 years old) ② Pregnancy ③ Those who cannot tolerate surgery due to other diseases ④ First episode of ITP, especially in children.
4.Immunosuppressive therapy: Applicable to those who have poor efficacy of glucocorticoids or splenectomy, and those who have contraindications to the use of glucocorticoids or splenectomy, but should not be the first choice.
5.Other treatment: Danazol is a synthetic androgen, which has synergistic effect with glucocorticoids, and its mechanism of action is related to immunomodulation and anti-estrogen. Amineptin, the efficiency of which has been reported to be up to 40%. In addition, Chinese medicine also has certain efficacy.
6.The treatment of emergency is applicable to: those with platelets below 20×109/L, those with severe and extensive bleeding, those suspected of having or having had intracranial bleeding, those who will perform surgery or delivery in the near future.
(1), platelet transfusion can be repeated according to the condition.
(2), Intravenous high-dose gammaglobulin. 0.4g/kgd, intravenous drip, 4-5 days as a course of treatment, can be repeated after one month. Or 1g/kgd with 2 days as a course of treatment, repeat after one month.
(3), Plasma replacement can effectively remove PAIg from the patient’s plasma.
(4), High-dose methylprednisolone, which can exert therapeutic effect by inhibiting the destruction of platelets by monocyte-macrophage system.