Primary thrombocytopenic purpura (ITP) is an acquired bleeding disorder caused by excessive platelet destruction with impaired maturation of megakaryocytes, with thrombocytopenia and bleeding from skin, mucous membranes and even internal organs as the main manifestations. It is also known as idiopathic thrombocytopenic purpura because more than 85% of the patients have IgG antibodies on the platelet or serum surface, and its development is related to autoimmunity, so it is also called autoimmune thrombocytopenic purpura. Some patients are combined with autoimmune hemolytic anemia, which is called Evans syndrome.
The incidence of ITP: this disease is a common bleeding disorder, the clinical classification into acute and chronic two types, the incidence is about 1/20,000, mostly seen in children and young adults, under 30 years of age accounted for 60-70%, more than 40 years of age not more than 10%, the onset of no geographical differences, the mortality rate is less than 1%, most of the deaths from visceral, especially intracranial hemorrhage. The prognosis is mostly good. The acute type is self-limiting, while the chronic type is rarely self-healing, prone to recurrent attacks, and the course of the disease can last for several years.
This disease belongs to the category of purpura and collapse of blood in Chinese medicine.
[Etiology and pathogenesis]
The etiology and pathogenesis of ITP are not fully understood, but are generally considered to be related to the following factors.
(a) Pathogenetic factors: The disease is an acquired bleeding disorder, and its pathogenesis is related to the following factors.
1, age factors: acute type is mostly seen in children aged 2-6 years; chronic type is mostly seen in adults.
2, gender factors: chronic type is more often young women, male: female incidence rate of 1:3-4; acute type gender differences are not obvious.
3, immune factors: the onset of chronic ITP is related to autoimmunity, the specific cause is not known. Acute ITP is associated with viral infections, including rubella virus, measles virus, cytomegalovirus, EBV, mumps virus, varicella, herpes zoster virus, hepatitis virus, etc. Even some live virus vaccinations can cause acute ITP by stimulating the immune response.
(B) Pathogenesis.
The basic link in the pathogenesis of ITP may be viral infection and other factors that produce immune complexes that bind to Fc receptors on platelet membranes and activate or stimulate an increase in anti-platelet antibodies (mainly PAIgG), causing the destruction of platelets and megakaryocytes, the main sites of destruction being the spleen, liver and bone marrow.
Acute ITP is caused by the production of antibodies related to the virus (antigen) in the body after viral infection, which then cross-react with platelet membranes, causing non-specific damage to platelets and clearance by the monocyte-macrophage system; or antiviral antibodies combine with the corresponding antibody progenitors to form immune complexes that attach to the platelet surface.
Chronic ITP occurs mainly by platelet antibody IgG (PAIgG) produced by the spleen, which first binds specifically to the relevant antigen on the platelet membrane through its Fab fragment, exposing the Fc fragment and binding to the Fc receptor of macrophages, causing platelet phagocytosis or destruction; in addition, immune complexes (CIC) bind to the Fc receptor on platelets through the Fc fragment on its IgG molecule and activates complement C3, which anchors C3 to platelets and is eventually recognized and phagocytosed by macrophages.
The role of cellular immunity in this disease is unclear. It is known that ITP patients have dysregulated helper and suppressor T cells and defective TA cell function.
According to traditional Chinese medicine, the etiology of ITP is the result of the internal incandescence of evil heat, burning the blood channels and forcing the blood to move delicately; or dampness and heat, which can cause the disease to be caused by the internal incandescence of evil heat, burning the blood channels and forcing the blood to move delicately; or dampness and heat, which can cause the blood to boil, injuring the blood channels and causing the blood to overflow outside the veins. The disease may be caused by the internal heat of dryness and wind-heat, or by heat illness that injures Yin, or by over-eating spicy and fried food that depletes Yin; or by labor that injures the kidneys and depletes Yin essence; or by deficiency of endowment and Yin deficiency in the body, and then by Yang Qi scops due to annoyance and labor, all of which can lead to the internal flourishing of deficiency fire that burns the Blood channels and causes the Blood to overflow outside the veins. Or inadequate endowment, spleen and kidney deficiency; or worry and tiredness injury to the spleen, fright, labor desire injury to the kidneys; or feel the evil of cold and damp; or after a serious illness, damage to the spleen and kidney Yang Qi, resulting in spleen deficiency is not the power of control, kidney deficiency is the failure to seal the function, can lead to blood overflow veins and this disease. There are also injuries caused by the seven emotions, liver qi stagnation, qi stagnation and blood stasis; or heat disease depletion of qi and yin, yang qi deficiency will be weak to push, yin blood deficiency will be difficult to blood flow; or long term disease into the ligament, qi stagnation and blood stasis; or blood out, stop and stay stasis, stasis blood internal obstruction of the veins and ligaments, new blood can not return to the meridian and overflow and become. In short, there are five mechanisms of the disease: heat enters the blood and blood, and blood heat is delusional; Yin deficiency and fire, and blood overflows; Qi deficiency does not take in, and blood overflows outside the veins; blood stasis blocks the veins, and blood does not return to the meridians; dampness and heat intermingle and steam, and the veins are damaged. The location of the disease is mainly in the skin and blood vessels, and its occurrence is related to the internal organs, especially the spleen, stomach, liver, lung and kidney. The spleen is the master of muscles, and it is in contact with the stomach. If the spleen and stomach are deficient in qi, the blood will overflow to the skin and become purple spots; if the liver does not store blood, or if the liver is depressed, the fire will burn the blood channels, which can cause the blood to overflow to the veins and become purple spots; if the kidney is deficient in qi, it will fail to seal and hide the blood; if the kidney is deficient in yin, the deficiency of fire will burn the channels, which can cause purple spots. In addition, the heart is the master of blood vessels, so excessive heart fire will force the blood to overflow; the lung is facing the hundred veins, and the outer skin and hair, so when the external evil enters the lung, it will often offend the lung first, which will spread the heat and burn the blood vessels, which can lead to purple spots. Acute ITP is mostly caused by external sensation, internal heat toxicity, heat into the blood; or diet, food stagnation and fire, or liver depression and fire, forcing the blood to move; or even depletion of qi and yin, turning into chronic; chronic ITP is often caused by insufficient endowment, spleen and kidney deficiency, or by external sensation or internal injury to diet, labor and fatigue, the seven emotions, resulting in deficiency of spleen, stomach, liver and kidney, or deficiency of fire and injury to the ligaments, qi deficiency and non-intake, after the blood is out, stasis of blood remains inside, every time due to sensation of evil or overexertion. After the blood is released, the blood stasis remains inside, and is triggered or exacerbated by the feeling of evil or overexertion, resulting in the evidence of deficiency of the root and the symptoms.
[Diagnosis]
I. Clinical manifestations
(a) Purpura is the main feature of ITP. The hemorrhage can occur in any part and organ, but mainly in the skin and mucous membrane. The bleeding spots vary in size, flat, mostly pinpoint-like, a few are large petechiae that do not fade when pressed, and are more common in the extremities. Gingival blood and epistaxis, genitourinary system also often bleed, and oral mucosal blood blisters often suggest severe reduction of platelets. Intracranial or retinal hemorrhage is less common and may result in dizziness, headache, vomiting, blurred vision, coma, or even death or blindness.
(b) The spleen is mostly not large or mildly enlarged.
(c) Acute type is common in children and may be seen in adults. The onset is most frequent in autumn and winter. There is often a history of respiratory or other systemic viral infections 1 to 3 weeks prior to the onset of the disease. The onset of the disease may be rapid, with fever, chills, and sudden onset of extensive and severe skin and mucosal hemorrhage or hematoma. The disease lasts from a few days to several months. A small number of cases may become chronic.
(d) Chronic type is usually seen in young and strong women, usually without a history of antecedent infection. The onset of the disease is slow and insidious, and skin bleeding is more common in the distal lower extremities. It is often recurrent and lasts for several months or years.
Laboratory and other tests
(A) platelets: platelet count is reduced in several examinations, often less than 20×109/L in acute type and chronic type, and less than 10×109/L when there is often extensive, spontaneous bleeding tendency; chronic type is mostly between 30-80×109/L, and often asymptomatic when it is higher than 50×109/L. Giant or malformed platelets are often seen.
(B) White blood cell count: mostly normal. In acute bleeding, there may be neutrophilia or leftward nuclear shift. Acute type may have eosinophilia or lymphocytosis.
(C) Red blood cells and hemoglobin: in severe bleeding, orthocytic anemia may be seen, and in long-term chronic bleeding, microcytic hypochromic anemia may be seen due to iron deficiency.
(D) Bone marrow picture: active proliferation, normal or increased number of megakaryocytes, impaired maturation, mainly granulocytes or nuclei, few or no platelets, platelets are rare; granulocytes and red blood cell system are basically normal.
(E) Increased platelet antibody IgG (PAIgG).
(vi) Shortened platelet life span: acute type may be less than a few hours, chronic type 1 day-3 days.
[Differential diagnosis]
(1) Secondary thrombocytopenia: In addition to bleeding symptoms, there are often features of the primary disease. Bone marrow examination can help in differential diagnosis. If infective thrombocytopenia has a clear history of infection and signs and symptoms of the primary disease, megakaryocytes in the bone marrow, and even leukocytes and red blood cell system can be reduced. In drug-derived thrombocytopenia, there is a clear history of drug use before the onset of the disease, and the bleeding stops within a few days after stopping the drug, and the platelet count returns to normal, if it does not return to normal within 7-10 days, drug-derived thrombocytopenia is basically excluded. Patients with remittent disease have more whole blood reduction, bone marrow image of granulocytes, red and megakaryocytes are reduced, and fatty components are increased. In hematologic malignancies, if platelets are reduced, there must be a significant increase in the number of naive cells of the corresponding cell system in the bone marrow.
Evans syndrome: In addition to thrombocytopenia and megakaryocyte maturation disorder, it is accompanied by autoimmune hemolysis and positive Coomb’s test.
Thrombotic thrombocytopenic purpura: In addition to thrombocytopenia, there may be neurological symptoms such as disorientation, drowsiness and convulsions, and hemolysis, or myocardial damage, but Coom’s test is negative.
Hereditary thrombocytopenic purpura: clinically it is difficult to distinguish from ITP, but patients often have family history, and family lineage investigation helps to diagnose.
3, allergic purpura: mostly infection, drug or food allergens can be found; while ITP cannot find the cause. The skin purpura is symmetrical, appear in batches, can be higher than the skin surface, often accompanied by itching, the extremities, especially the lower extremities mainly, can be accompanied by urticaria; while ITP is bleeding pinpoint, can be fused into pieces, irregular-shaped, scattered throughout the body, uneven distribution, not higher than the skin surface, generally not itchy, no paresthesia. There may be abdominal cramps with blood in the stool; in ITP, blood in the stool is seen without abdominal pain. There may be joint swelling and pain; ITP does not. Hematuria with nephritis may be present; in ITP, hematuria alone without nephritis is present. Blood clot retraction test is normal; ITP is poorly retracted. Platelet count is normal and eosinophils may be increased; in ITP, platelet count is decreased and eosinophils are normal. Bone marrow macrophages have no qualitative or quantitative changes; ITP shows impaired maturation or increased number of macrophages.
[Critical indicators]
1. Extensive or severe bleeding in the skin and mucous membranes.
2.Intracranial hemorrhage or fundus hemorrhage.
3.Large or persistent vaginal or nasal bleeding with more than hemorrhagic shock.
4. Platelet count less than 10×109/L.
[Treatment]
I. Western medical treatment
(I) Treatment principles
Remove the cause, control the bleeding symptoms, and reduce platelet destruction.
(B) Treatment measures
1, adrenocorticotropic hormone: corticotropic hormone can inhibit antibody production, inhibit antigen antibody reaction, inhibit mononuclear macrophage chemotaxis and phagocytosis to prevent platelet retention in the splenic sinus, thus reducing platelet destruction; it can also reduce capillary fragility, reduce bleeding; and stimulate bone marrow hematopoiesis. For the initial treatment of ITP, the use of hormones is generally advocated, and the dose should be large and the course of treatment should be short. The commonly used dose is 1mg-2mg per kg of body weight per day, and after 3-4 weeks, regardless of the efficacy, it should be reduced to gradually stop. The general method of dose reduction is to reduce 5mg per week after achieving remission until 20mg per day or less, so that platelets are maintained above 50×109/L. Maintenance treatment is generally not more than 6 months to avoid side effects. Failure to achieve remission after 6 weeks of treatment is considered a failure of corticosteroid therapy. Corticosteroids should not be used in large quantities for a long time to restore platelets to normal.
2. Danazol (Danazol): It is a synthetic androgen with few masculinizing side effects. It may raise the platelet count by suppressing T cells and making antibody production decrease. Dose: 0.2g each time, 3 times daily, reduce the dose to stop after 6 months of continuous use. In case of relapse, re-treatment is effective. It has the potential to replace corticosteroids as the first choice for ITP. It can also be used in combination with corticosteroids.
Splenectomy or splenic artery embolization: Splenectomy is an effective treatment for chronic ITP. Platelets can be rebounded during the operation, and can rise significantly 24 hours after the operation, reaching a peak in 1-2 weeks, and maintaining normal levels for more than 2 months is considered effective. The recent complete remission rate can reach 70%-80%; however, the relapse rate reaches 30-50%, which may be related to the presence of parasplenium or liver involved in platelet destruction. Splenic artery embolization has become more popular in recent years and is less invasive but less effective. Indications for splenectomy.
(i) Those who have been ineffective for more than six months by active medical treatment.
(ii) Those who are ineffective in corticosteroid treatment or require more than 30 mg/d to stop bleeding.
(iii) Those with contraindications to hormones.
④those with intracranial hemorrhage tendency who have been ineffective by active medical treatment.
⑤ Those who have severe bleeding within 6 months of pregnancy.
Contraindications.
① Those who are under 2 years of age.
②those with heart disease and other complications.
③Early cases of first onset.
④Late stage of pregnancy.
⑤ Patients with acute fulminant type.
4.Immunosuppressant; it is a third-line drug with large toxic side effects. Immunosuppressant indications.
① those with ineffective hormone or spleen excision.
② Those with hypersplenism and cannot cut the spleen. The use of vincristine 1mg-2mg per week for 4 weeks, platelets rise within 1-2 weeks, but after discontinuation of the drug, platelets can not be maintained; or cyclophosphamide 1.5mg-3mg per kg of body weight per day, divided into 3 oral doses, or 0.3g-0.6g per square meter of body surface area, intravenous injection, once every 3 weeks; or azathioprine 1mg-3mg per kg of body weight per day, oral, often requires 4 or azathioprine 1mg-3mg per kg of body weight per day, orally, often requiring more than 4 weeks to be effective; or cycloheximide A, 10mg per kg of body weight per day, divided into two doses, the disadvantage is expensive.
5.Tamoxifen: can compete with estrogen and T-cell binding to raise platelets. 10mg per dose, 3 times daily, taken orally. The effect is slow and it is advisable to use the drug continuously for more than 3 months, and then stop the drug 2 months after the platelets return to normal.
6.Component transfusion: Generally, it is only used for ITP emergency treatment or preparation for splenectomy or refractory ITP.
(1) Intravenous gammaglobulin: good efficacy, but high price. Mechanisms.
① Inhibition of platelet antibody production.
(ii) Closure of monocyte-macrophage Fc receptors.
③Protection of platelets from antibody coverage and sensitization.
④Clear the foci of viral infection. Dosage: 0.4g per kg of body weight for 5 days, or 0.5g per kg of body weight given periodically in case of thrombocytopenia.
(2) Plasma exchange: It can remove a large amount of platelet antibodies from plasma and bring about recent remission. Usage: 1000-3000ml of fresh plasma each time, at least 2-3 times in a row. The disadvantages are high cost and the tendency to produce homoimmune antibodies with repeated use.
(3) Concentrated platelets: Generally, it is not recommended because most of the platelets are destroyed by ITP transfusion, and the efficacy is poor and the cost is high. It is only used for emergency hemostasis or before splenectomy.
Chinese medicine treatment
(A) Characteristics of symptoms
The onset of ITP may be acute or slow, and the manifestations are mostly purple spots, epistaxis, epistaxis, epistaxis, blood in urine, and leakage, but also blood in cough, blood in stool, and in severe cases, the symptoms may be dangerous, such as moving the wind to close the orifice and violent blindness. In cases of real fire, the onset is rapid, the duration is short, the purple spots are purple-red in color, or fused into patches, with more distribution on the yang side of the limbs, or even all over the body, with symptoms of blood-heat delusion; in cases of deficiency fire, the onset is rapid or slow, the duration is short or long, the purple spots are reddish-red in color, with more distribution on the yin side of the limbs, with symptoms of yin deficiency and fire; in cases of qi deficiency, the onset is slow and the duration is long, with recurrent attacks, the purple spots are light red in color, with symptoms of spleen and kidney qi deficiency; in cases of blood stasis, the onset is rapid or slow, the purple spots are reddish-red in color, with symptoms of blood stasis. The onset of the disease may be acute or slow, with purple spots of dark color, and is accompanied by internal obstruction of blood stasis or Qi stagnation and blood stasis.
(II) Treatment points
Treatment of ITP should be based on stopping bleeding to treat the symptoms and identifying the evidence to treat the root cause. After the bleeding, the blood that leaves the meridian stays in the body, that is, stasis of blood, so stopping the bleeding and eliminating the spots is not only the symptom of the disease, but also the basic treatment. In terms of identifying and treating the root cause of the disease, for those with blood-heat delusion, it is advisable to clear heat and cool the blood; for those with yin deficiency and fire, it is also advisable to nourish yin and clear heat; for those with qi deficiency, it is advisable to combine qi and blood; for those with blood stasis, it is also advisable to invigorate blood and nourish luo. For those who have both symptoms, the above mentioned rules should be applied flexibly according to their specific identification.
(III) Treatment by type
1. Blood-heat delusion
The onset of the disease is urgent, with subcutaneous petechiae, purple-red, or fused into patches, or even all over the body, fever and night, heart trouble or thirst, constipation, yellow urine, often accompanied by epistaxis, epistaxis, blood in urine, blood in stool, dark red and sticky blood, red-red and vivid tongue, thin yellow coating, and string or thin slippery pulse.
Treatment Clearing heat and detoxifying the toxin, cooling the blood and eliminating blemishes.
Example formula Rhizoma Dihuang Tang, Qingying Tang, and Hepatitis Tang.
2.Yin deficiency and fire
Main symptoms Scattered petechiae and petechiae on the skin, bright red or bruises, sometimes light and sometimes heavy, more bleeding at night, or with epistaxis, epistaxis, or excessive menstruation, leakage of menstrual flow, fever in the heart, hot flashes and night sweats, especially in the afternoon and at night, or soreness and weakness of the waist and knees, dryness of the mouth and throat, red tongue with little coating, fine pulse.
Treatment Nourishing Yin and clearing heat, nourishing the luo and stopping bleeding.
Example formula: Xie Gen San combined with Er Zhi Wan.
Contingency measures
Compound Salvia injection 10ml-20ml with saline 250ml in intravenous drip.
Raw pulse injection 20ml-30ml plus physiological saline 250ml intravenously.
Blood Kang oral solution 10ml-20ml, 3 times-4 times daily, orally.
3.Qi deficiency does not take in
Main symptoms: Purple spots with light red color or scattered distribution, recurrent attacks, aggravated by exertion, dizziness and fatigue, palpitation and shortness of breath, pale or yellow face, dullness and loose stools, pale mouth and low voice, pale tongue or teeth marks, white fur, weak pulse.
Treatment Strengthening the spleen and nourishing the blood, benefiting Qi and regulating blood.
Example formula: Gui Shen Tang.
Commonly used drugs Radix Codonopsis, Radix Astragali, Atractylodes Macrocephala, Poria, Radix Rehmanniae Sinensis, Haematoxylin, Fritillariae Sinensis, Palmariae Sinensis, Panax Ginseng, Rhizoma Polygonati, Colla Corii Asini.
Contingency measures
Astragalus injection 10ml-30ml plus 5% glucose injection in intravenous drip.
Lishen injection 10ml-20ml plus saline in intravenous drip.
Ginseng and wheat injection 20ml-30ml plus saline intravenously.
4.Blood stasis blocking the ligament
Main symptoms: Subcutaneous purple spots, dark bruises, or subcutaneous or submuscular hematomas, or hypochondriacal masses, dark stools, or dark face, dark eyes, dark lips and nails, black menstrual stasis or brownish black like coffee, purple and dark tongue or stasis spots, or coarse and black veins under the tongue, with astringent or fine pulse.
Treatment To activate blood circulation, resolve blood stasis, and stop bleeding.
Example formula Tao Hong Si Wu Tang.
Commonly used herbs: peach kernel, safflower, angelica, Chuanxiong, red peony, raw earth, panax ginseng, rhubarb, fried pu huang, purple pearl grass, cyperus root, cyperus root.
Emergency measures
Haikang Oral Liquid 10ml-20ml, 3 times daily, orally.
Yunnan Baiyao 0.5g-1g, 3 times a day, orally.
Zi Di Combination 50ml or Zi Di Ning Xue San 4-8g, 3 times a day, orally.
Compound Salvia injection 16ml-20ml, add saline in intravenous drip.
5.Dampness and heat
Main symptoms Purple spots, or epistaxis, epistaxis, or even blood in urine or stool, with deep red or bright red blood, or body heat, nausea, dullness, yellow urine, heavy head and body, sticky mouth, red tongue, yellow greasy coating, moist pulse.
Treatment Clearing heat and removing dampness, cooling the blood and stopping bleeding.
Example formula Ermiao San combined with Sophora Jiao Wan.
Commonly used drugs Atractylodes macrocephala, Phellodendron, Sophora japonica, Radix Scutellariae, Radix Scutellariae, Fructus Fenugreek, Citrus aurantium, Rhizoma Bamboo, Rhizoma Sugae, Rhizoma Huanglian, Rhizoma Polygonatum, Rhizoma Dioscorea, Rhizoma Bupleurum, Rhizoma Cyperus, Poria cocos.
Contingency measures
Shuanghuanglian powder injection 2g-3g with saline in intravenous drip.
Qingkailing injection 20ml-30ml plus saline in intravenous drip.