I. Etiology and pathogenesis
The acute form of the disease occurs after the recovery of acute viral upper respiratory tract infections and the formation of antigen-antibody complexes in the body, in which the FC fragments on the antibody molecules bind to FC receptors on platelets. Platelets with immune complexes attached are easily destroyed within the mononuclear phagocyte system, so the disease is also considered to be an immune complex disease, suggesting a possible link between the reduction of platelets and the immune response caused by the primary infection.
Another theory suggests that exogenous infection alters the structure of the platelet membrane, making it antigenic and producing anti-self platelet antibodies in the body (autoimmune disease), or that antiviral antibodies have a crossed immune response to platelet membrane antigens.
About half of the patients with the chronic form have been found to have anti-platelet antibodies in their sera, belonging to immunoglobulins G, M, A, C3, C4, etc. IgG is the most common, and it is thought that PAIgG may be the true anti-platelet antibody.
Platelet surface-bound immunoglobulins, namely platelet surface-associated immunoglobulins (PAIg), bind to platelet-specific antigens through the Fab fragment on their IgG molecules and to macrophage receptors through their FC fragments, causing platelets to be phagocytosed and destroyed.
The amount of PAIgG is positively correlated with the disease. Platelets and megakaryocytes share common antigenicity, and megakaryocytes can also be directly damaged.
Spleen factor: In vivo scintigraphy with radioisotope-labeled antibodies on platelets showed that about 60% of bound antibodies and platelets were destroyed in the spleen; about 15% were destroyed in the liver, mainly by platelets with high amounts of bound antibodies, so the latter were mostly seen in severe cases.
In addition, the spleen is the main site of autoantibody synthesis.
Estrogen action: Estrogen inhibits platelet production and promotes phagocytosis of antibody-bound platelets by mononuclear macrophages.
II. Clinical manifestations
1. Acute type
Mostly in children under 10 years old, with no difference between the two sexes. Most of them have a history of viral infections, mostly respiratory infections, rubella, measles and chickenpox; also after vaccination. The incubation period between infection and purpura is mostly within 1 to 3 weeks. The acute form is rare in adults, often associated with drugs, and is more severe than in children. The onset is rapid and fever may be present.
The skin bleeding is mainly skin and mucous membrane bleeding, often more severe, skin bleeding in petechiae of different sizes, uneven distribution, more in the extremities. Mucosal bleeding includes epistaxis, gum bleeding, and blood blisters in the oral tongue mucosa. Gastrointestinal and urinary tract hemorrhage, subconjunctival hemorrhage, and a few retinal hemorrhages are often present. Spinal cord or intracranial hemorrhage is common and can cause lower limb paralysis or intracranial hypertension manifestations, which can be life-threatening.
If the patient has headache and vomiting, be alert to the possibility of intracranial hemorrhage. The course of the disease is mostly self-limiting, and more than 80% can resolve on their own, with an average duration of 4 to 6 weeks. A small number of cases can be prolonged or become chronic for more than a few years. Acute type accounts for less than 10% of adult ITP.
2. Chronic type
The chronic type accounts for 80% of ITP, mostly between 20 and 50 years old, and 3 to 4 times as many women as men. The onset of the disease is insidious. Patients may have persistent bleeding or recurrent episodes, and some show a local bleeding tendency, such as recurrent epistaxis or excessive menstruation.
Petechiae and petechiae can occur on any part of the skin and mucous membranes, but are more frequent on the distal extremities. Gastrointestinal and urinary tract bleeding may be present. Deep hematomas may also occur after trauma. Intracranial hemorrhage is less common, but can still occur during acute attacks. The spleen may occasionally be palpable during deep inspiration.
Platelets between (10-50)×109/L may have varying degrees of spontaneous bleeding, and platelets less than 10×109/L often have severe bleeding, and the patient is in good general condition except for bleeding symptoms.
Three, the diagnostic criteria
1. multiple laboratory tests for thrombocytopenia.
2.Spleen not enlarged or only mildly enlarged.
3, normal increase in megakaryocytes with maturation disorders on bone marrow examination.
4, having any of the following 5 points.
(1) prednisone therapy is effective.
(2) Effective splenic function removal.
(3) Increased PAIgG.
(4) Increased PAC3.
(5) Shortened platelet lifespan.
5. Exclude secondary thrombocytopenia.
Immune thrombocytopenia can also be seen in lupus erythematosus, tuberculosis, nodular disease, hyperthyroidism, chronic thyroiditis and autoimmune anemia (Evans syndrome).
Laboratory tests
1. Blood picture
Acute type platelets are significantly reduced, mostly below 20×109/L. When the bleeding is severe, it may be accompanied by anemia, and the white blood cells may be increased. Occasionally there is eosinophilia. In chronic cases, platelets are mostly in the range of 30 to 80×109/L, and giant malformed platelets are common.
2.Bone marrow picture
In acute type, the number of megakaryocytes is normal or increased, mostly of naive type, with smooth cell edges, no protrusions, little cytoplasm and large granules. In the chronic type, megakaryocytes are usually significantly increased, and granular megakaryocytes are increased, but the cytoplasm has fewer granules and is more basophilic.
3.Immunological examination
At present, most domestic and foreign countries use direct binding test, such as nuclein labeling, fluorescent labeling or enzyme-linked anti-serum PAIg assay. Domestic application of enzyme-linked immunosorbent assay to determine PAIgG, PAIgM and PA-C3 positive rate of 94%, 35%, 39%, respectively, in patients with ITP. The degree of increase was negatively correlated with the platelet count. PAIgM is more common in the acute form. Anti-platelet autoantibodies can also be detected in meganuclear surface cells.
4.Other
Prolonged bleeding time, positive bundle arm test, poor clot contraction, reduced platelet adhesion and aggregation, shortened life span as measured by 51Cr or 111In labeled platelets.
V. Western medical treatment
1, acute type and severe cases should be hospitalized
Restrict activities, enhance care, and avoid trauma. Prohibit all drugs that affect platelet aggregation to avoid aggravating bleeding.
Symptomatic treatment with hemostatic drugs.
(1) Hemostatin: It can reduce capillary permeability, cause vasoconstriction, shorten bleeding time, and also strengthen platelet adhesion function and accelerate clot contraction.
(2) Anloha: It can stabilize the acidic mucopolysaccharide in the blood vessels and their surrounding tissues, and make the blood vessels less brittle.
(3) Anti-fibrinolytic drugs: choose as appropriate.
2.Adrenocorticotropic hormone
Adrenocorticotropic hormone is preferred for heavy bleeding, which has obvious effect on raising platelets and preventing bleeding. However, after stopping the drug, half of the cases can be relapsed, and continued use is still effective.
The mechanism of action of adrenocorticosteroids may be: inhibition of phagocytosis of the mononuclear macrophage system, which prolongs the life of antibody-coated platelets; improvement of capillary osmotic fragility and improvement of bleeding. Prednisone is commonly used clinically.
Dose; in acute type, higher doses are required to prevent intracranial bleeding until platelets reach safe levels. Chronic type generally need 2-3 weeks to show effect, the beginning of the full dose, and then gradually reduce the dose to 5-10mg daily or / alternate day oral, maintenance period of up to 4-6 months.
If the bleeding is heavy, intravenous injection of hydrocortisone or dexamethasone is effective. If the liver function is poor or long-term prednisone is ineffective, switching to prednisolone can sometimes be effective. Long-term users should add anabolic hormones (such as nandrolone phenylpropionate) as appropriate.
3.Splenectomy
Splenectomy is one of the effective treatments for ITP.
Indications.
(1) Chronic ITP, where active medical treatment for 6 months is ineffective.
(2) Poor efficacy of adrenocorticotropic hormone, or those who need to be maintained with higher doses (30-40 mg/d).
(3) Contraindicated for hormone or immunosuppressive applications.
(4) 51Cr marker platelet examination, if platelets are mainly blocked in the spleen, the efficiency of splenectomy is up to 90%, if blocked in the liver, 70% of splenectomy is ineffective. The efficiency of splenectomy is up to 70-90%, and the postoperative recurrence rate is 9.6-22.7%. The long-term effect is 50-60%.
4.Immunosuppressant
Cyclophosphamide is orally administered, and it usually takes 2-6 weeks to be effective, with a remission rate of 30-40% and strong myelosuppressive effects. Azathioprine has a remission rate of about 40% and requires long-term use. Vincristine (VCR) or vincristine (VLB) can selectively bind to microtubule globulin of monocytes and inhibit their phagocytosis and C3 receptor function, once in 7-10 days, 3-4 times as a course of treatment.
5.Immunoglobulin
(1) Inhibit the production of autoantibodies.
(2) Inhibit the function of FC receptors of monocyte macrophages.
(3) Protect platelets from being attached by platelet antibodies.
6.Danazol
It is a synthetic androgen, the course of treatment ≥ 2 months, pregnant women are prohibited, regular liver function checks.
7, platelet transfusion
For patients with life-threatening bleeding or preoperative preparation. Each transfusion of platelets 2.5U (each unit is equivalent to 200ml of platelets contained in whole blood), platelets can be increased by 10 × 109 / L. Such as the infusion of immunoglobulin and then platelet transfusion, platelets can be extended life. Platelet transfusion is likely to cause the recipient to produce homologous antibodies, affecting the effect of transfusion.
8.Plasma exchange
It is suitable for acute severe patients to remove some anti-platelet antibodies in a short time. However, chronic ITP is generally ineffective.