Idiopathic thrombocytopenic purpura (ITP), also known as primary or immune thrombocytopenic purpura, has been named “primary immune thrombocytopenia” by a consensus of experts.
It is characterized by a significant decrease in peripheral platelets and impaired maturation of bone marrow megakaryocytes. Clinical manifestations include bleeding from the skin or viscera, and in severe cases, bleeding from other areas such as nasal bleeding, gum bleeding, excessive menstrual flow in women or severe vomiting of blood, hemoptysis, blood in stool, blood in urine, etc. Intracranial hemorrhage is a fatal cause of this disease.
The therapeutic effects of hormones are generally considered to be.
(i) reduce capillary permeability and decrease bleeding tendency;
(2) reduce the immune response, and reduce the production of PAIgG and inhibit the phagocytosis of antibody-bearing platelets by splenic mononuclear macrophages.
Therefore, the bleeding phenomenon can be improved more quickly after the early application of large amounts of hormones in ITP patients. At present, we still advocate that hormone therapy should be given to patients with moderate disease within 1 month of onset (especially within 2 weeks) or patients with severe disease despite long onset. The principle of drug administration is early, large amount and short course. Generally, prednisone 60mg/m2・d (2mg/kg・d) should be given orally in two to three doses or once in the morning. If the bleeding is serious, prednisone can be used up to 120mg/m2・d orally or hydrocortisone 400mg/m2・d or flumethasone 10~15mg/m2・d intravenously, and then change to prednisone 60mg/m2・d when the bleeding is better.
However, there are some side effects of hormone therapy, as follows
1. Hyperadrenocorticism
(1) Adrenal androgenesis (adrenal sexual syndrome): hairiness, hair loss, acne, low voice, amenorrhea, uterine atrophy, clitoral enlargement, breast reduction and muscle increase. Sexual desire can be increased. Hirsutism can be the only sign in mild cases.
Cushing’s syndrome: full-moon face, polycythemia with centripetal obesity, prominent supraclavicular fossa and dorsocervical fat pad (buffalo back); distal limbs and fingers often very elongated, muscle wasting and weakness. The skin is thin and atrophic, and the wounds do not heal easily and are easily bruised. Purple lines are seen on the abdomen. Hypertension, kidney stones, osteoporosis, decreased glucose tolerance, poor resistance to infection and mental disorders are common. Cessation of linear growth is characteristic of children. Irregular menstruation is common in women. In adrenal tumors, in addition to cortisol, increased androgen production can lead to hirsutism, temporal hair loss and other androgenic signs in women.
Long-term use of corticosteroids in excess of physiological doses can cause disorders of water, salt, sugar, protein and fat metabolism, manifesting as centripetal obesity, full-moon face, acne, hirsutism, weakness, swelling, hypertension, hyperlipidemia and hyperglycemia. Generally, no special treatment is needed and can gradually disappear on its own and return to normal after stopping the drug. If necessary, treatment with anti-hypertensive and anti-diabetic drugs, a low-salt, low-sugar, high-protein diet and the addition of potassium chloride can reduce symptoms. Hypertension, arteriosclerosis, edema, cardiac and renal insufficiency and diabetes mellitus patients should be prohibited.
2.Obstruct the absorption of calcium
①Decreased secretion of gonadotropins: weaken the secretion of pituitary gonadotropins (luteinizing hormone and follicle stimulating hormone), causing a decrease in the concentration of estradiol, estrone, dehydroandrosterone and luteinizing hormone in the blood. Dehydroandrosterone, androstenedione and estrogen secreted by the adrenal glands are suppressed due to adrenocorticotropic hormone and adrenal atrophy. Decreased secretion of androstenedione causes a decrease in estrone levels (under normal conditions, estrone is aromatized from androstenedione in the surrounding adipose tissue). These anabolic hormones may play an important role in the pathogenesis of glucocorticoid-induced osteoporosis.
(ii) Secondary hyperparathyroidism: attributed to inhibition of intestinal calcium absorption and negative calcium homeostasis due to high urinary calcium.
(iii) Inhibition of intestinal calcium absorption: this effect is not well related to vitamin D. The role of corticosteroid-vitamin D interactions in corticosteroid-induced changes in calcium absorption is not known.
(iv) Decreased calcium reabsorption by the renal tubules: fasting hypercalciuria and elevated blood PTH are seen. Hypercalciuria is due to increased bone resorption and decreased renal tubular calcium reabsorption.
Corticosteroids promote proteolysis and inhibit protein synthesis, leading to a negative nitrogen balance and increased excretion of calcium and phosphorus, and can also impede calcium absorption. Inhibition of bone formation, collagen synthesis is increased during the first 24 hours in the presence of supraphysiological concentrations of corticosteroids, but is clearly inhibited after 48 hours. After 48 hours of exposure, DNA synthesis was reduced and tissue sections confirmed reduced mitosis.
Osteocalcin synthesis is inhibited by corticosteroids, and serum osteocalcin levels are low in patients treated with corticosteroids. Enhanced bone resorption, which involves the production of new osteoclasts for cell replication, is inhibited by high doses and prolonged exposure. Due to its anti-vitamin D effect, bone formation is impaired, leading to osteoporosis and, in severe cases, spontaneous fractures. Long-term users of corticosteroids should supplement vitamin D and calcium salts.
3. Inducing or aggravating infection
The long-term application of corticosteroids may induce new infections or latent infections in the body and even spread to the whole body, especially for patients with low resistance. Serious systemic infections, including serious deep mycobacterial infections and Pseudomonas aeruginosa infections, occur after long-term application of larger doses of corticosteroids. Skin, oral, intestinal, biliary, and urinary tract infections develop during drug administration and progress to bacterial or mycobacterial sepsis. These infections often have insidious symptoms and mild clinical manifestations, but the consequences are extremely serious. The use of corticosteroids should be prohibited for those who have had viral infections such as tuberculosis and chickenpox.
4. Affect wound healing, induce and aggravate ulcers
Corticosteroids can promote protein decomposition, delay the formation of granulation tissue, and hinder the healing of trauma or surgical wounds and ulcers. It can increase secretion of gastric acid and pepsin, reduce secretion of gastric juice and decrease resistance of gastric mucosa, so it can induce or aggravate gastric and duodenal ulcers, and even cause bleeding or perforation of peptic tract.
5.Central nervous symptoms
The symptoms are euphoria, agitation, insomnia, and individual cases may induce psychosis. In children, it can cause convulsions when applied in high doses. Seizures can also be induced in epileptic patients. Corticosteroids should be used with caution or prohibited in psychiatric and epileptic patients.
6. Adrenal cortex atrophy or insufficiency
Longer-term application of this drug may cause negative feedback effects due to higher than normal levels of corticosteroids in the body, inhibiting the secretion of adrenocorticotropic hormones in the subthalamic and anterior pituitary gland, reducing endogenous corticosteroid secretion and even leading to adrenal atrophy. In case of stressful situations, such as major surgery, trauma, bleeding and severe infection, weakness, dizziness, nausea, vomiting, hypotension, hypoglycemia and even coma or shock may occur. In order to avoid the above, the daily maintenance amount should be reduced as much as possible, and early discontinuation of the drug should be strived for when possible.
7. Rebound phenomenon and discontinuation symptoms
After long-term use of drugs, if the dose is reduced and stopped too quickly, sometimes the original symptoms will quickly reappear and worsen, called “rebound phenomenon”. Some people may have symptoms that are not present in the original disease, such as myalgia, myalgia, arthralgia, etc., which are called discontinuation symptoms. Therefore, when stopping the medication, do not stop abruptly.