Immune thrombocytopenia (ITP) is a group of immune-mediated bleeding disorders. It is characterized by a decrease in platelet production due to impaired maturation of platelet-producing megakaryocytes in the bone marrow and the appearance of autoantibodies specific to platelet surface membrane glycoproteins, resulting in excessive platelet destruction and shortened platelet survival time, which eventually leads to extensive bleeding in the skin, mucosa and internal organs. The disease can be clinically classified into acute and chronic forms.
I. What are the symptoms of ITP patients?
Most patients with acute ITP have a history of upper respiratory tract and other infections, especially viral infections, 1 to 2 weeks before the onset of the disease. Petechiae and petechiae on the skin of the whole body, nasal bleeding, gum bleeding, oral mucosa, and tongue bleeding are also more common, and in severe cases, blood blisters and hematomas may be formed. Chronic ITP has a relatively insidious onset and is mostly detected by chance during routine blood tests. The disease is mild and limited, but it is prone to recurrent attacks, and severe visceral bleeding is less common. If the disease lasts for more than six months, some patients can feel a mass in the left upper abdomen, which is a sign of mild splenomegaly.
Second, what are the treatment methods for ITP?
First, rest should be paid attention to those with severe bleeding tendency. When platelets are lower than 20×109/L, they should be strictly bedridden, avoid trauma, and start treatment immediately to try to control bleeding quickly. Glucocorticoids are generally the first choice of treatment, which can reduce the destruction of platelets by autoantibodies, with a recent efficiency of 80%. Splenectomy may be considered if the patient is not suitable for hormone use or if hormone therapy is ineffective for 3-6 months. If glucocorticoids or splenectomy are not effective, then immunosuppressive therapy can be considered, which can reduce the formation of autoantibodies and reduce the destruction of platelets, but it is generally not preferred. There are also other drugs that can treat ITP, such as danazol (a synthetic androgen that has synergistic effects with glucocorticoids) and amineptin.
What tests should be done in patients with ITP?
Secondly, bone marrow routine should be done, which shows normal or increased megakaryocyte count, but impaired maturation, mainly granular megakaryocyte proliferation; in addition, platelet antibody examination, patients can see elevated serum anti-platelet antibodies (PAIgG, PAIgM, PAIgA) and platelet-associated complement PAC3; there can also be platelet The levels of CD3+T, CD3+CD4+T and CD3+CD8+T are significantly lower in T-cell subsets, while CD3+CD8+T is significantly higher.
Under which circumstances can splenectomy be performed for ITP?
Splenectomy can be considered when ITP is present in the following situations.
1, those who have been ineffective with hormone therapy for 3 to 6 months.
2, Those whose hormone therapy is effective and relapses after stopping or reducing the dose.
3.Those who need larger doses of hormone, such as with prednisone >30mg/d, to maintain platelets above 50×109/L and make the bleeding symptoms disappear. For acute type, if there is intracranial hemorrhage aura, or serious bleeding from other important organs, emergency splenectomy is also feasible when available.
V. What is the effect of splenectomy for ITP and what are the complications?
The factors that affect the efficacy of splenectomy are.
1. age, the remission rate of splenectomy is higher in children than in adults, and the efficacy of splenectomy is worst in the elderly.
2. gender, the remission rate after splenectomy is higher in women than in men
3, better outcome for those with a disease duration of less than 6 months
4. the remission rate after splenectomy is high in those with effective preoperative hormones
5, associated with the rate and peak of postoperative platelet rise.
6. poor efficacy in those with markedly elevated preoperative platelet-related antibody PAIgG and those with postoperative PAIgG still high.
7. the presence of parasplenic or residual splenic tissue is a cause of recurrence
8. the efficacy of splenectomy is good in those whose platelets are destroyed in the spleen. The complication rate of splenectomy is usually less than 5%, mainly infections, such as pneumonia, subphrenic abscess, bacteraemia or sepsis.
VI. What other diseases can coexist with ITP?
ITP is an autoimmune disease and is often accompanied by other autoimmune diseases or is an early manifestation of other autoimmune diseases. Other immune diseases that can coexist with ITP include rheumatoid arthritis, scleroderma, periarteritis nodosa, dry syndrome, myasthenia gravis, ulcerative colitis, interstitial pneumonia, etc. ITP can also occur with autoimmune thyroid diseases (hyperthyroidism, Hashimoto’s disease) and with hematologic tumors (chronic lymphocytic leukemia, Hodgkin’s disease, B-cell lymphoma).
VII. What are the causes of ITP?
Bacterial or viral infections are closely related to the development of ITP. In patients with acute ITP, there is often a history of upper respiratory tract infection about 2 weeks before the onset of the disease, while in patients with chronic ITP, the disease is often aggravated by infection. It is currently believed that excessive phagocytosis and destruction of autoantibody-sensitized platelets by the mononuclear macrophage system is the main mechanism of ITP pathogenesis. The spleen is also the main site of autoantibody production and an important site of platelet destruction. it is common in women, and estrogen has been found to inhibit platelet production and/or enhance phagocytosis of antibody-bound platelets by the monocyte-macrophage system.
What diseases should ITP be differentiated from?
First of all, secondary thrombocytopenic purpura should be excluded, such as various splenomegaly diseases, bone marrow invasive diseases, chemical and drug allergy and poisoning, hemolytic anemia, etc. All these conditions can be accompanied by thrombocytopenia and should be carefully examined to find out the cause. Next is aplastic anemia, which can manifest itself as three major symptoms: fever, anemia, and bleeding. Total white blood cells and neutrophils are mostly reduced, and reticulocytes are not high. The bone marrow red and granulocyte system has reduced blood production, and megakaryocytes are reduced or extremely difficult to detect. There is also the differentiation of acute leukemia, ITP especially needs to be distinguished from leukemia without an increase in leukocytes, which can be diagnosed by the presence of naive leukocytes of all stages in blood smears and bone marrow examination. Sometimes it should also be distinguished from the immune disease lupus erythematosus.
What are the emergency management methods for ITP? What are the conditions for which they are applicable?
Acute management can be done by
1. platelet transfusion: adults are given 10-20 units/session, which can be repeated according to the condition, and single-collected platelets are used as much as possible in places with conditions.
2, intravenous immunoglobulin: 0.4g/Kg, intravenous drip, 4 to 5 days as a course of treatment. 1 month later can be repeated.
3, high-dose methylprednisolone: 1g/d, intravenous injection, 3-5 times as a course of treatment, can play a therapeutic role by inhibiting the monocyte-macrophage system.
4, plasma exchange within 3 to 5 days, more than 3 times in a row, each time with 3000 ml of plasma exchange, also has certain therapeutic effect.
5.Emergency splenectomy.
Applicable to.
1.Those with platelets below 20×109/L.
2, those with severe and extensive bleeding.
3.Those who are suspected of having or have had intracranial hemorrhage.
4. Those who will perform surgery or delivery in the near future.
X. What is the effect of glucocorticoids in treating ITP and what should be noted when using them?
Generally speaking, glucocorticoids are the first choice of treatment, and the recent efficiency is about 80%. Prednisone 1mg/(kg.d) is commonly used in divided doses or as a dose. In severe cases, the equivalent amount of dexamethasone or methylprednisolone is given intravenously, and after improvement, it is given orally. After the platelets rise to normal or close to normal, the dosage is gradually reduced (5mg every 1-2 weeks), and finally 5-10mg/d is used for maintenance treatment for 3-6 months. Foreign scholars mostly believe that ITP patients with no obvious bleeding tendency and platelet count >30×109//L can be left untreated.
XI. What are the indications for ITP treatment with immunosuppressive drugs? What are the commonly used drugs?
Indications.
1.Inadequate efficacy of glucocorticoids or splenectomy.
2. Contraindication to the use of glucocorticoids or splenectomy.
3. Combined with glucocorticoids to improve the efficacy and reduce the dosage of glucocorticoids.
Commonly used drugs.
1, vincristine: the most commonly used, 1mg per time, once a week, intravenous injection, 4-6 weeks as a course of treatment.
2.Cyclophosphamide: 50~100mg/d, orally, 3~6 weeks as a course of treatment, gradually reduce the dosage after the emergence of efficacy, maintain 4~6 weeks.
3. Azathioprine: 100-200mg/d orally for 3-6 weeks, followed by 25-50mg/d for 8-12 weeks.
4.Cyclosporine: mainly used for the treatment of refractory ITP. 250～500mg/d orally, with a maintenance dose of 50～100mg/d, which can be maintained for more than six months.
5.Tacrolimus：Tacrolimus (FK506) is a macrolide antibiotic extracted from the ferment of Streptomyces, mainly through the inhibition of interleukin-2 release, the role of comprehensive inhibition of T lymphocytes, with a strong immunosuppressive effect, its immunosuppressive effect is about 10 to 100 times that of cyclosporine (CsA). Tacrolimus 5-10mg/d orally, maintain blood concentration at 5-20 ng/mL.
Twelve, the use of immunosuppressive drugs may have what adverse reactions?
Common drugs such as.
1, cyclophosphamide caused by bone marrow suppression, although more common, but generally easier to recover. Liver function is more common, and a few patients may also have dizziness, restlessness, hallucinations and other adverse reactions. Long-term application may cause testicular atrophy in men, sperm deficiency, amenorrhea in women, ovarian fibrosis, and fetal malformation during pregnancy. Occasional gastric ulcers, gastric bleeding, etc..
2, cyclosporine mild with headache, limb tremor, sensory disorders, etc. are common, moderate with visual impairment.
3.Tacrolimus, because of its narrow therapeutic index and large individual differences, its clinical adverse reactions are also more obvious, the most important of which are nephrotoxicity and neurotoxicity. Under normal conditions, tacrolimus is safe and effective when the blood concentration is between 5 and 20 ng/mL, and it is likely to produce dose-dependent adverse reactions when it exceeds 20 ng/mL. Therefore, in order to minimize the toxic side effects, maximize the efficacy and ensure the success of immunosuppression program, the clinical use of tacrolimus should closely monitor the patient’s blood concentration, blood creatinine, urine volume and liver function, and then make reasonable calculations according to the patient’s liver and kidney function, administer the appropriate amount of drug, and formulate a reasonable individualized and safe treatment plan to reduce the occurrence of adverse reactions.
XIII. What are the characteristics of Chinese medicine in the treatment of ITP?
According to Chinese medicine, this disease is mostly in the category of “blood evidence” and “purple spot (grape disease)”. Its occurrence is mostly related to the internal invasion of evil heat or internal heat or Yang Qi deficiency that can’t take in blood. In acute cases, the key to the pathogenesis lies in the incandescence of blood heat, while in chronic cases, it is due to the deficiency of qi and inability to regulate the blood. In addition, blood leaving the meridian becomes “stasis blood”, so stasis blood blocking the ligaments is often an important pathological link for both types. Therefore, for the acute type, TCM clinics mostly intend to cool the Blood and invigorate the Blood, nourish Yin and clear heat, while for the chronic type, the methods of benefiting Qi and invigorating Blood, nourishing Blood and regulating Blood are used, often combined with the addition of flavors to take into account the individual differences of patients and other pathological changes.
Is there any good food therapy for ITP treatment?
ITP can be caused by poor diet, depression, internal injury to vital energy, or yin deficiency, and is characterized by bleeding from the skin and mucous membranes (internal organs, etc.). The diet of solid heat type should be cool and clear, such as eating mung bean soup and other things to clear the poisonous heat, avoiding or eating less warm and pungent products to avoid the occurrence of purple spots in succession, making the poisonous heat more abundant. For deficiency-heat type, cool and moist food is recommended, such as duck meat to nourish Yin and cool blood, and avoid or cautiously use warm, dry and hot products to avoid excessive bleeding, and the evidence of deficiency-heat disturbance such as agitation and restlessness. The Qi deficiency type can eat cinnamon meat and other products that benefit the Qi and blood, and avoid or lessen the consumption of river crab and other cooling and qi-damaging products to avoid the occurrence of shortness of breath, body fatigue, mental fatigue, blood bleeding and other evidence of Qi not taking blood.